Is ALG13 p.Asp608His (c.1822G>C) pathogenic?

ALG13 p.Asp608His (c.1822G>C) is classified Conflicting classifications of pathogenicity in ALG13 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.1604); Very rare (popmax 0.00436%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG13 p.Asp608His (c.1822G>C)?

ALG13 p.Asp608His (c.1822G>C) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 36 (ClinVar).

How common is ALG13 p.Asp608His (c.1822G>C) in the general population?

ALG13 p.Asp608His (c.1822G>C) is very rare (popmax 0.00436%, nfe) (gnomAD).

What do computational predictors say about ALG13 p.Asp608His (c.1822G>C)?

AlphaMissense predicts likely benign (score 0.1604) — an in-silico prediction, not a clinical call.

ALG13 p.Asp608His

c.1822G>C · rs374870130 · VCV1100622

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00436%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1604	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -5.67	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 4.3	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.27 · regional, not allelic
Overall
CADD	13.44	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 0.00436% European (non-Finnish) · 39/895,033 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00322% 39/1,209,302 alleles · very rare exomes 37/1,098,016 · genomes 2/111,286 · joint denominator

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: ALG13
Protein: p.Asp608His
Coding: c.1822G>C
MANE Select: NM_001099922
dbSNP: rs374870130
Type: single nucleotide variant
Location: chrX:111726901 (GRCh38)
Structure: AlphaFold pLDDT 54.42

Full ALG13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 36

Similar variants

ALG13 p.Asp608= Likely benign ★ same residue
ALG13 p.Asn107Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG13 c.2458-1G>A Uncertain significance ★★ same condition
ALG13 c.2695+4G>A Uncertain significance ★★ same condition
ALG13 c.2932+6T>C Uncertain significance ★★ same condition
ALG13 c.834+3A>G Uncertain significance ★★ same condition
ALG13 c.932+2T>C Uncertain significance ★★ same condition
ALG13 p.Ala1044Thr 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/alg13-p-asp608his (accessed [today's date]).

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