Is ALG14 p.Val6Ile (c.16G>A) pathogenic?

ALG14 p.Val6Ile (c.16G>A) is classified Conflicting classifications of pathogenicity in ALG14 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-24). AlphaMissense: likely benign (0.0736); Very rare (popmax 0.00237%, nfe); Associated with intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies.

How common is ALG14 p.Val6Ile (c.16G>A) in the general population?

ALG14 p.Val6Ile (c.16G>A) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about ALG14 p.Val6Ile (c.16G>A)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

ALG14 p.Val6Ile

Q: What condition is associated with ALG14 p.Val6Ile (c.16G>A)?

ALG14 p.Val6Ile (c.16G>A) is associated with intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies, congenital myasthenic syndrome 15, myopathy, epilepsy, and progressive cerebral atrophy (ClinVar).

c.16G>A · rs756921157 · VCV1356542

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -3.4
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,180,016 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00198% 32/1,613,952 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)grpmax	0.00237%	42,143
African / African-American	0.00133%	74,918

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ALG14
Protein: p.Val6Ile
Coding: c.16G>A
MANE Select: NM_144988
dbSNP: rs756921157
Type: single nucleotide variant
Location: chr1:95072883 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06

Full ALG14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 15 myopathy, epilepsy, and progressive cerebral atrophy

Similar variants

ALG14 p.Ala13Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Arg109Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn61Asp Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn61Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn82Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Glu110Lys Uncertain significance ★★ same condition
ALG14 p.Glu179Lys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/alg14-p-val6ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown