Is ALG1 p.Ala204Glu (c.611C>A) pathogenic?

ALG1 p.Ala204Glu (c.611C>A) is classified Uncertain significance in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.1379); Very rare (popmax 0.00212%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG1 p.Ala204Glu (c.611C>A)?

ALG1 p.Ala204Glu (c.611C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ALG1 p.Ala204Glu (c.611C>A) in the general population?

ALG1 p.Ala204Glu (c.611C>A) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about ALG1 p.Ala204Glu (c.611C>A)?

AlphaMissense predicts likely benign (score 0.1379) — an in-silico prediction, not a clinical call.

ALG1 p.Ala204Glu

c.611C>A · rs201011560 · VCV3110491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1379 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1379	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	16.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,180,024 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,614,034 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,201
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,088

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: ALG1
Protein: p.Ala204Glu
Coding: c.611C>A
MANE Select: NM_019109
dbSNP: rs201011560
Type: single nucleotide variant
Location: chr16:5077516 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 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

Similar variants

ALG1 p.Ala204Val Uncertain significance ★ ⚠ same residue
ALG1 p.Ala204= Likely benign ★ same residue
ALG1 p.Ala360Val Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Gln342Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG1 p.Ala278Thr Uncertain significance ★★ ⚠ same condition
ALG1 p.Arg257Gln Uncertain significance ★★ ⚠ same condition
ALG1 p.Asn311Lys Uncertain significance ★★ ⚠ same condition
ALG1 p.Asn80His 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/alg1-p-ala204glu (accessed [today's date]).

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