Is ALG5 p.Leu11Val (c.31C>G) pathogenic?

ALG5 p.Leu11Val (c.31C>G) is classified Likely benign in ALG5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-04-17). AlphaMissense: likely benign (0.0777); Rare (popmax 0.124%, nfe); Associated with ALG5-related disorder.

What condition is associated with ALG5 p.Leu11Val (c.31C>G)?

ALG5 p.Leu11Val (c.31C>G) is associated with ALG5-related disorder (ClinVar).

How common is ALG5 p.Leu11Val (c.31C>G) in the general population?

ALG5 p.Leu11Val (c.31C>G) is rare (popmax 0.124%, nfe) (gnomAD).

What do computational predictors say about ALG5 p.Leu11Val (c.31C>G)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

ALG5 p.Leu11Val

c.31C>G · rs147574138 · VCV3040312

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.124%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG5-related disorder

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.78	unconstrained · MANE · 49 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	15.9	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 0.124% European (non-Finnish) · 1,444/1,166,328 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.107% 1,699/1,580,554 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.281%	356
European (non-Finnish)grpmax	0.124%	808
Remaining individualsnot grpmax-eligible	0.0999%	1,001
African / African-American	0.0236%	4,229
Admixed American	0.00181%	55,260

Finnish 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: ALG5
Protein: p.Leu11Val
Coding: c.31C>G
MANE Select: NM_013338
dbSNP: rs147574138
Type: single nucleotide variant
Location: chr13:36999270 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.29

Full ALG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG5-related disorder

Similar variants

ALG5 p.Arg212Cys Uncertain significance ★ ⚠ same condition
ALG5 p.Ala19Ser Uncertain significance ⚠ same condition
ALG5 p.Arg79Gln Uncertain significance ⚠ same condition
ALG5 p.Ala18= Benign same condition
ALG5 p.Ala2= Likely benign same condition
ALG5 p.Gly12= Benign same condition
ALG5 p.Thr249= Likely benign same condition
ALG5 p.Trp60Arg Likely benign 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/alg5-p-leu11val (accessed [today's date]).

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