Is ALG3 p.Ala65Val (c.194C>T) pathogenic?

ALG3 p.Ala65Val (c.194C>T) is classified Uncertain significance in ALG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.2169); Very rare (popmax 0.00155%, afr).

How common is ALG3 p.Ala65Val (c.194C>T) in the general population?

ALG3 p.Ala65Val (c.194C>T) is very rare (popmax 0.00155%, afr) (gnomAD).

What do computational predictors say about ALG3 p.Ala65Val (c.194C>T)?

AlphaMissense predicts likely benign (score 0.2169) — an in-silico prediction, not a clinical call.

ALG3 p.Ala65Val

c.194C>T · rs1336047164 · VCV445988

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2169 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00155%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2169	likely benign
REVEL	0.634	indeterminate
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.62	donor gain · deltas
Pangolin	Δ0.44	loss · gain 0.34 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,742 bp · p 0.14 · regional, not allelic
Overall
CADD	35.0	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 0.00155% African / African-American · 1/64,648 alleles

Filtering AF 3.6e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000241% 3/1,246,132 alleles · very rare exomes 2/1,098,278 · genomes 1/147,854 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00155%	64,648
European (non-Finnish)	0.000219%	456,442

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: ALG3
Protein: p.Ala65Val
Coding: c.194C>T
MANE Select: NM_005787
dbSNP: rs1336047164
Type: single nucleotide variant
Location: chr3:184248747 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full ALG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG3 c.444+1G>T Likely pathogenic ★★ same type
ALG3 p.Arg171Gln Pathogenic/Likely pathogenic ★★ same type
ALG3 p.Arg266Cys Pathogenic ★★ same type
ALG3 p.Arg354Cys Likely pathogenic ★★ same type
ALG3 p.Arg354His Pathogenic/Likely pathogenic ★★ same type
ALG3 p.Asn174Ser Likely pathogenic ★★ ⚠ same type
ALG3 p.Gly55= Pathogenic/Likely pathogenic ★★ same type
ALG3 p.Ile69Thr Likely pathogenic ★★ same type

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/alg3-p-ala65val (accessed [today's date]).

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