Is ASAH1 p.Ala337Val (c.1010C>T) pathogenic?

ASAH1 p.Ala337Val (c.1010C>T) is classified Uncertain significance in ASAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-10). AlphaMissense: likely benign (0.2041); Very rare (popmax 0.00133%, afr).

How common is ASAH1 p.Ala337Val (c.1010C>T) in the general population?

ASAH1 p.Ala337Val (c.1010C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ASAH1 p.Ala337Val (c.1010C>T)?

AlphaMissense predicts likely benign (score 0.2041) — an in-silico prediction, not a clinical call.

ASAH1 p.Ala337Val

c.1010C>T · rs2537915670 · VCV2124156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2041	likely benign
REVEL	0.519	indeterminate
SaProt	LLR -11.77	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.37	unconstrained · MANE · 27 kb · p 6.4e-16 · regional, not allelic
Overall
CADD	22.7	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 0.00133% African / African-American · 1/75,044 alleles

Overall 6.84e-05% 1/1,461,882 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: ASAH1
Protein: p.Ala337Val
Coding: c.1010C>T
MANE Select: NM_177924
dbSNP: rs2537915670
Type: single nucleotide variant
Location: chr8:18059372 (GRCh38)
Gene constraint: LOEUF 1.435 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.97 · 2 PDB
Residue 337: a disulfide bond; a UniProt-annotated variant site (in smapme; loss of protein abundance; the corresponding mrna is not detected and probably degraded); an α-helix

Full ASAH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASAH1 c.1098+1G>T Pathogenic/Likely pathogenic ★★ same type
ASAH1 c.125+1G>A Pathogenic ★★ same type
ASAH1 c.457+4A>G Pathogenic/Likely pathogenic ★★ same type
ASAH1 c.648+1G>C Likely pathogenic ★★ same type
ASAH1 c.786-2A>G Likely pathogenic ★★ same type
ASAH1 p.Arg254Gly Pathogenic ★★ same type
ASAH1 p.Arg296Ter Pathogenic ★★ same type
ASAH1 p.Arg333Cys Pathogenic/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/asah1-p-ala337val (accessed [today's date]).

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