Is ACRBP p.Val405Phe (c.1213G>T) pathogenic?

ACRBP p.Val405Phe (c.1213G>T) is classified Uncertain significance in ACRBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-14). AlphaMissense: likely benign (0.1001); Absent from gnomAD v4.1.

How common is ACRBP p.Val405Phe (c.1213G>T) in the general population?

ACRBP p.Val405Phe (c.1213G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACRBP p.Val405Phe (c.1213G>T)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

ACRBP p.Val405Phe

c.1213G>T · rs368787320 · VCV2611995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.71	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 -3.9	GERP -2.9
Regional constraint	o/e 0.95	unconstrained · MANE · 7,246 bp · p 0.19 · regional, not allelic
Overall
CADD	6.025	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACRBP
Protein: p.Val405Phe
Coding: c.1213G>T
MANE Select: NM_032489
dbSNP: rs368787320
Type: single nucleotide variant
Location: chr12:6640387 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.09
Residue 405: the 'pro-acr binding' region

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

Similar variants

ACRBP p.Ala192Val Uncertain significance ★ ⚠ same type
ACRBP p.Ala244Thr Uncertain significance ★ ⚠ same type
ACRBP p.Ala24Thr Uncertain significance ★ ⚠ same type
ACRBP p.Ala324Gly Uncertain significance ★ ⚠ same type
ACRBP p.Ala345Val Uncertain significance ★ ⚠ same type
ACRBP p.Arg110Cys Uncertain significance ★ ⚠ same type
ACRBP p.Arg162Cys Uncertain significance ★ ⚠ same type
ACRBP p.Arg242Gln 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/acrbp-p-val405phe (accessed [today's date]).

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