Is ABT1 p.Ala68Val (c.203C>T) pathogenic?

ABT1 p.Ala68Val (c.203C>T) is classified Uncertain significance in ABT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely benign (0.1049); Very rare (popmax 0.00381%, nfe).

How common is ABT1 p.Ala68Val (c.203C>T) in the general population?

ABT1 p.Ala68Val (c.203C>T) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about ABT1 p.Ala68Val (c.203C>T)?

AlphaMissense predicts likely benign (score 0.1049) — an in-silico prediction, not a clinical call.

ABT1 p.Ala68Val

c.203C>T · VCV4636490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1049 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1049	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.82	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 4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 1,659 bp · p 0.01 · regional, not allelic
Overall
CADD	19.87	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 0.00381% European (non-Finnish) · 45/1,180,056 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00279% 45/1,614,122 alleles · very rare

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.Ala68Val
Coding: c.203C>T
MANE Select: NM_013375
Type: single nucleotide variant
Location: chr6:26597185 (GRCh38)
Gene constraint: LOEUF 1.2 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08
Residue 68: 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.Ala92Val Uncertain significance ★ ⚠ same type
ABT1 p.Ala93Val 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-ala68val (accessed [today's date]).

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