Is ASB13 p.Ala124Val (c.371C>T) pathogenic?

ASB13 p.Ala124Val (c.371C>T) is classified Uncertain significance in ASB13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely pathogenic (0.9734); Very rare (popmax 0.00535%, nfe).

How common is ASB13 p.Ala124Val (c.371C>T) in the general population?

ASB13 p.Ala124Val (c.371C>T) is very rare (popmax 0.00535%, nfe) (gnomAD).

What do computational predictors say about ASB13 p.Ala124Val (c.371C>T)?

AlphaMissense predicts likely pathogenic (score 0.9734) — an in-silico prediction, not a clinical call.

ASB13 p.Ala124Val

c.371C>T · rs139621358 · VCV3130100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9734	likely pathogenic
REVEL	0.888	moderately pathogenic-leaning
SaProt	LLR -14.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 26 kb · p 0.23 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00535% European (non-Finnish) · 63/1,177,558 alleles

Filtering AF 0.00427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00416% 67/1,609,064 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00535%	18,691
Remaining individualsnot grpmax-eligible	0.00482%	20,741
African / African-American	0.00134%	74,690

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: ASB13
Protein: p.Ala124Val
Coding: c.371C>T
MANE Select: NM_024701
dbSNP: rs139621358
Type: single nucleotide variant
Location: chr10:5651224 (GRCh38)
Gene constraint: LOEUF 1.686 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.60

Full ASB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB13 p.Ala189Thr Uncertain significance ★ ⚠ same type
ASB13 p.Ala190Ser Uncertain significance ★ ⚠ same type
ASB13 p.Ala210Asp Uncertain significance ★ ⚠ same type
ASB13 p.Ala210Pro Uncertain significance ★ ⚠ same type
ASB13 p.Ala263Thr Uncertain significance ★ ⚠ same type
ASB13 p.Ala58Thr Uncertain significance ★ ⚠ same type
ASB13 p.Arg160Gln Uncertain significance ★ ⚠ same type
ASB13 p.Arg211Gln 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/asb13-p-ala124val (accessed [today's date]).

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