Is RHBDF2 p.Ala162Pro (c.484G>C) pathogenic?

RHBDF2 p.Ala162Pro (c.484G>C) is classified Uncertain significance in RHBDF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely pathogenic (0.8767); Absent from gnomAD v4.1.

How common is RHBDF2 p.Ala162Pro (c.484G>C) in the general population?

RHBDF2 p.Ala162Pro (c.484G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RHBDF2 p.Ala162Pro (c.484G>C)?

AlphaMissense predicts likely pathogenic (score 0.8767) — an in-silico prediction, not a clinical call.

RHBDF2 p.Ala162Pro

c.484G>C · rs754079094 · VCV2026831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8767 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8767	likely pathogenic
REVEL	0.497	indeterminate
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 7,466 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	27.4	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 A191P vs ClinVar A162P) — verify the residue.

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: RHBDF2
Protein: p.Ala162Pro
Coding: c.484G>C
MANE Select: NM_001005498
dbSNP: rs754079094
Type: single nucleotide variant
Location: chr17:76478994 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 5 PDB
Residue 191 UniProt numbering: the 'involved in interaction with frmd8' region

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

Similar variants

RHBDF2 p.Ala162Ser Uncertain significance ★ ⚠ same residue
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

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-ala162pro (accessed [today's date]).

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