Is RHBDF2 p.Ile796Val (c.2386A>G) pathogenic?

RHBDF2 p.Ile796Val (c.2386A>G) is classified Likely benign in RHBDF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.0635); Rare (popmax 0.192%, sas).

How common is RHBDF2 p.Ile796Val (c.2386A>G) in the general population?

RHBDF2 p.Ile796Val (c.2386A>G) is rare (popmax 0.192%, sas) (gnomAD).

What do computational predictors say about RHBDF2 p.Ile796Val (c.2386A>G)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

RHBDF2 p.Ile796Val

c.2386A>G · rs768744728 · VCV2889074

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.192%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.34	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 1.3	GERP -3.6, phastCons 0.83
Regional constraint	o/e 0.61	unconstrained · MANE · 2,421 bp · p 3e-15 · regional, not allelic
Overall
CADD	7.59	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 I825V vs ClinVar I796V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.192% South Asian · 174/90,570 alleles

Filtering AF 0.169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.16%

Overall 0.011% 177/1,611,236 alleles · rare exomes 172/1,459,100 · genomes 5/152,136 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.192%	521
Remaining individualsnot grpmax-eligible	0.00481%	20,788

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.Ile796Val
Coding: c.2386A>G
MANE Select: NM_001005498
dbSNP: rs768744728
Type: single nucleotide variant
Location: chr17:76471731 (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-ile796val (accessed [today's date]).

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