Is ASPHD2 p.Val53Met (c.157G>A) pathogenic?

ASPHD2 p.Val53Met (c.157G>A) is classified Uncertain significance in ASPHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.1571); Very rare (popmax 0.00267%, afr).

How common is ASPHD2 p.Val53Met (c.157G>A) in the general population?

ASPHD2 p.Val53Met (c.157G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ASPHD2 p.Val53Met (c.157G>A)?

AlphaMissense predicts likely benign (score 0.1571) — an in-silico prediction, not a clinical call.

ASPHD2 p.Val53Met

c.157G>A · rs140657637 · VCV2331593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1571 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1571	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 548 bp · p 0.03 · regional, not allelic
Overall
CADD	22.1	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 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00217% 35/1,613,676 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,463
European (non-Finnish)	0.00263%	38,066
South Asian	0.0022%	45,540

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: ASPHD2
Protein: p.Val53Met
Coding: c.157G>A
MANE Select: NM_020437
dbSNP: rs140657637
Type: single nucleotide variant
Location: chr22:26433772 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 81.08

Full ASPHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASPHD2 p.Ala47Val Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg154Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg159Gln Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg341Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg43Lys Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg84Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Asn129Ser Uncertain significance ★ ⚠ same type
ASPHD2 p.Asn264Ser 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/asphd2-p-val53met (accessed [today's date]).

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