Is ASB1 p.Ala85Val (c.254C>T) pathogenic?

ASB1 p.Ala85Val (c.254C>T) is classified Uncertain significance in ASB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). AlphaMissense: likely pathogenic (0.9824); Very rare (popmax 0.00314%, nfe).

How common is ASB1 p.Ala85Val (c.254C>T) in the general population?

ASB1 p.Ala85Val (c.254C>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about ASB1 p.Ala85Val (c.254C>T)?

AlphaMissense predicts likely pathogenic (score 0.9824) — an in-silico prediction, not a clinical call.

ASB1 p.Ala85Val

c.254C>T · VCV3788212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9824	likely pathogenic · top 7% in ASB1
REVEL	0.715	pathogenic-leaning
SaProt	LLR -14.72	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 7.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.01 · regional, not allelic
Overall
CADD	28.4	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 0.00314% European (non-Finnish) · 37/1,180,022 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00242% 39/1,613,982 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,893
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: ASB1
Protein: p.Ala85Val
Coding: c.254C>T
MANE Select: NM_001040445
Type: single nucleotide variant
Location: chr2:238435773 (GRCh38)
Gene constraint: LOEUF 0.951 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.61

Full ASB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB1 p.Ala11Gly Uncertain significance ★ ⚠ same type
ASB1 p.Ala216Val Uncertain significance ★ ⚠ same type
ASB1 p.Arg141Trp Uncertain significance ★ ⚠ same type
ASB1 p.Arg144Cys Uncertain significance ★ ⚠ same type
ASB1 p.Arg144His Uncertain significance ★ ⚠ same type
ASB1 p.Arg156Gln Uncertain significance ★ ⚠ same type
ASB1 p.Arg165Ser Uncertain significance ★ ⚠ same type
ASB1 p.Arg186Gln 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/asb1-p-ala85val (accessed [today's date]).

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