Is ALG10 p.Ala12Asp (c.35C>A) pathogenic?

ALG10 p.Ala12Asp (c.35C>A) is classified Uncertain significance in ALG10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-17). AlphaMissense: likely pathogenic (0.9293); Very rare (popmax 0.000424%, nfe).

How common is ALG10 p.Ala12Asp (c.35C>A) in the general population?

ALG10 p.Ala12Asp (c.35C>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ALG10 p.Ala12Asp (c.35C>A)?

AlphaMissense predicts likely pathogenic (score 0.9293) — an in-silico prediction, not a clinical call.

ALG10 p.Ala12Asp

c.35C>A · rs1488967375 · VCV2403382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9293	likely pathogenic · top 9% in ALG10
REVEL	0.186	benign-leaning
SaProt	LLR -14.73	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 3.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 4,312 bp · p 0.0095 · regional, not allelic
Overall
CADD	26.3	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 0.000424% European (non-Finnish) · 5/1,180,018 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,026 alleles · very rare

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.Ala12Asp
Coding: c.35C>A
MANE Select: NM_032834
dbSNP: rs1488967375
Type: single nucleotide variant
Location: chr12:34022634 (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-ala12asp (accessed [today's date]).

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