Is ABT1 p.Ala93Val (c.278C>T) pathogenic?

ABT1 p.Ala93Val (c.278C>T) is classified Uncertain significance in ABT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.091); Ultra-rare (popmax 0.0164%, mid).

How common is ABT1 p.Ala93Val (c.278C>T) in the general population?

ABT1 p.Ala93Val (c.278C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ABT1 p.Ala93Val (c.278C>T)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

ABT1 p.Ala93Val

c.278C>T · VCV4189002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -8.04	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 3.1	GERP 1.5, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 1,659 bp · p 0.01 · regional, not allelic
Overall
CADD	17.93	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000682% 11/1,613,412 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,858
African / African-American	0.00534%	18,728
Remaining individualsnot grpmax-eligible	0.0016%	62,446
European (non-Finnish)	0.00017%	589,821

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: ABT1
Protein: p.Ala93Val
Coding: c.278C>T
MANE Select: NM_013375
Type: single nucleotide variant
Location: chr6:26597950 (GRCh38)
Gene constraint: LOEUF 1.2 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08
Residue 93: the rrm domain

Full ABT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABT1 p.Ala122Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala234Thr Uncertain significance ★ ⚠ same type
ABT1 p.Ala25Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala3Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala68Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala92Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala9Val Uncertain significance ★ ⚠ same type
ABT1 p.Arg120His 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/abt1-p-ala93val (accessed [today's date]).

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