Is RHBDF2 p.Pro398Ser (c.1192C>T) pathogenic?

RHBDF2 p.Pro398Ser (c.1192C>T) is classified Uncertain significance in RHBDF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: ambiguous (0.5026); No allele count reported in gnomAD v4.1 (AN 1,596,480).

How common is RHBDF2 p.Pro398Ser (c.1192C>T) in the general population?

RHBDF2 p.Pro398Ser (c.1192C>T) is no allele count reported in gnomAD v4.1 (AN 1,596,480) (gnomAD).

What do computational predictors say about RHBDF2 p.Pro398Ser (c.1192C>T)?

AlphaMissense predicts ambiguous (score 0.5026) — an in-silico prediction, not a clinical call.

RHBDF2 p.Pro398Ser

c.1192C>T · VCV3631118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5026 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,480)

Computational evidence

Protein change
AlphaMissense	0.5026	ambiguous
REVEL	0.538	indeterminate
SaProt	LLR -12.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 7,466 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	27.5	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 P427S vs ClinVar P398S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,596,480). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RHBDF2
Protein: p.Pro398Ser
Coding: c.1192C>T
MANE Select: NM_001005498
Type: single nucleotide variant
Location: chr17:76475065 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 5 PDB
Residue 427 UniProt numbering: an α-helix

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

Similar variants

RHBDF2 p.Pro398= Likely benign ★ 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-pro398ser (accessed [today's date]).

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