Is ABRACL p.Val3Met (c.7G>A) pathogenic?

ABRACL p.Val3Met (c.7G>A) is classified Uncertain significance in ABRACL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely pathogenic (0.8407); Ultra-rare (popmax 0.0354%, nfe).

How common is ABRACL p.Val3Met (c.7G>A) in the general population?

ABRACL p.Val3Met (c.7G>A) is ultra-rare (popmax 0.0354%, nfe) (gnomAD).

What do computational predictors say about ABRACL p.Val3Met (c.7G>A)?

AlphaMissense predicts likely pathogenic (score 0.8407) — an in-silico prediction, not a clinical call.

ABRACL p.Val3Met

c.7G>A · rs200480448 · VCV2345443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8407 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0354%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8407	likely pathogenic
REVEL	0.357	indeterminate
SaProt	LLR -12.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 8,739 bp · p 0.5 · regional, not allelic
Overall
CADD	29.3	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 0.0354% European (non-Finnish) · 418/1,180,052 alleles

Filtering AF 0.0325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0315%

Overall 0.0305% 493/1,614,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0946%	1,057
Remaining individualsnot grpmax-eligible	0.0368%	2,717
European (non-Finnish)grpmax	0.0354%	2,823
Admixed American	0.015%	6,668
African / African-American	0.0133%	7,495
Finnishnot grpmax-eligible	0.00625%	16,008
East Asian	0.00223%	44,902

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABRACL
Protein: p.Val3Met
Coding: c.7G>A
MANE Select: NM_021243
dbSNP: rs200480448
Type: single nucleotide variant
Location: chr6:139034167 (GRCh38)
Gene constraint: LOEUF 1.243 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 94.81 · 1 PDB
Residue 3: an α-helix

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

Similar variants

ABRACL p.Ala22Thr Uncertain significance ★ ⚠ same type
ABRACL p.Arg16Cys Uncertain significance ★ ⚠ same type
ABRACL p.Arg16Pro Uncertain significance ★ ⚠ same type
ABRACL p.Asp23Glu Uncertain significance ★ ⚠ same type
ABRACL p.Glu13Lys Uncertain significance ★ ⚠ same type
ABRACL p.Gly69Arg Uncertain significance ★ ⚠ same type
ABRACL p.Gly69Asp Uncertain significance ★ ⚠ same type
ABRACL p.His71Leu 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/abracl-p-val3met (accessed [today's date]).

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