Is ALG10 p.Met36Val (c.106A>G) pathogenic?

ALG10 p.Met36Val (c.106A>G) is classified Uncertain significance in ALG10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: ambiguous (0.4931); Ultra-rare (popmax 0.0178%, eas).

How common is ALG10 p.Met36Val (c.106A>G) in the general population?

ALG10 p.Met36Val (c.106A>G) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about ALG10 p.Met36Val (c.106A>G)?

AlphaMissense predicts ambiguous (score 0.4931) — an in-silico prediction, not a clinical call.

ALG10 p.Met36Val

c.106A>G · VCV4270073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4931 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4931	ambiguous
REVEL	0.267	benign-leaning
SaProt	LLR -11.46	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 3.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 4,312 bp · p 0.0095 · regional, not allelic
Overall
CADD	28.1	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 0.0178% East Asian · 8/44,848 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00149% 24/1,613,786 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,606
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00134%	74,806
European (non-Finnish)	0.000932%	107,271

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: ALG10
Protein: p.Met36Val
Coding: c.106A>G
MANE Select: NM_032834
Type: single nucleotide variant
Location: chr12:34022705 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.51

Full ALG10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG10 p.Ser243= Benign ★★ same type
ALG10 p.Thr134= Benign ★★ same type
ALG10 p.Val269Ile Benign ★★ same type
ALG10 c.369+1G>T Likely pathogenic ★ same type
ALG10 p.Met61Val Likely pathogenic ★ ⚠ same type
ALG10 p.Ala11Asp Uncertain significance ★ ⚠ same type
ALG10 p.Ala11Thr Uncertain significance ★ ⚠ same type
ALG10 p.Ala125Thr Uncertain significance ★ ⚠ 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/alg10-p-met36val (accessed [today's date]).

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