Is RHBDF2 p.Arg335= (c.1005G>T) pathogenic?

RHBDF2 p.Arg335= (c.1005G>T) is classified Likely benign in RHBDF2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-21). Ultra-rare (popmax 0.0307%, afr); Associated with RHBDF2-related disorder.

What condition is associated with RHBDF2 p.Arg335= (c.1005G>T)?

RHBDF2 p.Arg335= (c.1005G>T) is associated with RHBDF2-related disorder (ClinVar).

How common is RHBDF2 p.Arg335= (c.1005G>T) in the general population?

RHBDF2 p.Arg335= (c.1005G>T) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

RHBDF2 p.Arg335=

c.1005G>T · rs142836136 · VCV3047763

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Conditions

RHBDF2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.97	GERP -3.9, phastCons 0.001
Overall
CADD	7.997	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,956 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00149% 24/1,613,856 alleles · ultra-rare exomes 13/1,461,580 · genomes 11/152,276 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,259
Admixed American	0.00167%	60,014

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.Arg335=
Coding: c.1005G>T
MANE Select: NM_001005498
dbSNP: rs142836136
Type: single nucleotide variant
Location: chr17:76476940 (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

Disease context

RHBDF2-related disorder

Similar variants

RHBDF2 p.Arg335Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
RHBDF2 p.Ile157Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
RHBDF2 p.Pro160Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
RHBDF2 c.*3G>A Likely benign same condition
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

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-arg335 (accessed [today's date]).

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