Is ASPG p.Val263Met (c.787G>A) pathogenic?

ASPG p.Val263Met (c.787G>A) is classified Likely benign in ASPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-03). AlphaMissense: likely benign (0.1144); Very rare (popmax 0.00659%, sas).

How common is ASPG p.Val263Met (c.787G>A) in the general population?

ASPG p.Val263Met (c.787G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about ASPG p.Val263Met (c.787G>A)?

AlphaMissense predicts likely benign (score 0.1144) — an in-silico prediction, not a clinical call.

ASPG p.Val263Met

c.787G>A · VCV4155436

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1144	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -2.1, phastCons 0.89
Regional constraint	o/e 0.93	unconstrained · MANE · 27 kb · p 0.058 · regional, not allelic
Overall
CADD	7.255	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 0.00659% South Asian · 6/91,074 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00062% 10/1,612,456 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,179
African / African-American	0.00267%	37,465
European (non-Finnish)	0.00017%	589,887

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: ASPG
Protein: p.Val263Met
Coding: c.787G>A
MANE Select: NM_001080464
Type: single nucleotide variant
Location: chr14:104104337 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 2 PDB
Residue 263: the asparaginase/glutaminase domain; the 'asparaginase' region

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

Similar variants

ASPG p.Asp223= Benign ★★ same type
ASPG c.1620+1G>A Uncertain significance ★ same type
ASPG p.Ala315Gly Uncertain significance ★ ⚠ same type
ASPG p.Ala315Val Uncertain significance ★ ⚠ same type
ASPG p.Ala332Val Uncertain significance ★ ⚠ same type
ASPG p.Ala442Thr Uncertain significance ★ ⚠ same type
ASPG p.Ala4Thr Uncertain significance ★ ⚠ same type
ASPG p.Ala537Ser 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/aspg-p-val263met (accessed [today's date]).

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