Is RHBDF2 p.Ala332Val (c.995C>T) pathogenic?

RHBDF2 p.Ala332Val (c.995C>T) is classified Benign/Likely benign in RHBDF2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-25). AlphaMissense: likely benign (0.2668); Rare (popmax 0.753%, afr).

How common is RHBDF2 p.Ala332Val (c.995C>T) in the general population?

RHBDF2 p.Ala332Val (c.995C>T) is rare (popmax 0.753%, afr) (gnomAD).

What do computational predictors say about RHBDF2 p.Ala332Val (c.995C>T)?

AlphaMissense predicts likely benign (score 0.2668) — an in-silico prediction, not a clinical call.

RHBDF2 p.Ala332Val

c.995C>T · rs144193184 · VCV1658032

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2668 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.753%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2668	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -4.24	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 7,466 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A361V vs ClinVar A332V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.753% African / African-American · 565/75,076 alleles

Filtering AF 0.701% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.681%

Overall 0.0398% 643/1,613,974 alleles · rare exomes 321/1,461,580 · genomes 322/152,394 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.753%	133
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Admixed American	0.0483%	2,070
Middle Eastern	0.0165%	6,050
South Asian	0.0022%	45,543
European (non-Finnish)	0.000339%	295,010

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: RHBDF2
Protein: p.Ala332Val
Coding: c.995C>T
MANE Select: NM_001005498
dbSNP: rs144193184
Type: single nucleotide variant
Location: chr17:76476950 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 5 PDB

Full RHBDF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RHBDF2 p.Ile157Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
RHBDF2 c.151-27G>T Uncertain significance ★★ ⚠ same type
RHBDF2 c.151-86G>A Uncertain significance ★★ ⚠ same type
RHBDF2 p.Ala397Ser Uncertain significance ★★ ⚠ same type
RHBDF2 p.Ala700Thr Uncertain significance ★★ ⚠ same type
RHBDF2 p.Ala725Val Uncertain significance ★★ ⚠ same type
RHBDF2 p.Arg113His Uncertain significance ★★ ⚠ same type
RHBDF2 p.Arg205His 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/rhbdf2-p-ala332val (accessed [today's date]).

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