Is RHOB p.Ser73Phe (c.218C>T) pathogenic?

RHOB p.Ser73Phe (c.218C>T) is classified Conflicting classifications of pathogenicity in RHOB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2022-08-25). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1; Associated with RHOB-related disorder.

What condition is associated with RHOB p.Ser73Phe (c.218C>T)?

RHOB p.Ser73Phe (c.218C>T) is associated with RHOB-related disorder (ClinVar).

How common is RHOB p.Ser73Phe (c.218C>T) in the general population?

RHOB p.Ser73Phe (c.218C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RHOB p.Ser73Phe (c.218C>T)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

RHOB p.Ser73Phe

c.218C>T · rs550750241 · VCV1344805

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

RHOB-related disorder

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic
REVEL	0.534	indeterminate
SaProt	LLR -13.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.86, phastCons 1
Regional constraint	o/e 0.26	constrained · MANE · 239 bp · p 5.4e-15 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: RHOB
Protein: p.Ser73Phe
Coding: c.218C>T
MANE Select: NM_004040
dbSNP: rs550750241
Type: single nucleotide variant
Location: chr2:20447683 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI 0.23 (gnomAD)
Structure: AlphaFold pLDDT 92.54 · 3 PDB
Residue 73: an α-helix

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

Disease context

RHOB-related disorder

Similar variants

RHOB p.Ala116Thr Uncertain significance ★ ⚠ same type
RHOB p.Gln52Glu Uncertain significance ★ ⚠ same type
RHOB p.Gly50Ser Uncertain significance ★ ⚠ same type
RHOB p.Ile151Ser Uncertain significance ★ ⚠ same type
RHOB p.Ile190Met Uncertain significance ★ ⚠ same type
RHOB p.Ile23Thr Uncertain significance ★ ⚠ same type
RHOB p.Met82Ile Uncertain significance ★ ⚠ same type
RHOB p.Pro101Leu 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/rhob-p-ser73phe (accessed [today's date]).

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