Is RHAG p.Phe47Ser (c.140T>C) pathogenic?

RHAG p.Phe47Ser (c.140T>C) is classified Uncertain significance in RHAG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-30). AlphaMissense: likely benign (0.0945); Very rare (popmax 0.00659%, sas).

How common is RHAG p.Phe47Ser (c.140T>C) in the general population?

RHAG p.Phe47Ser (c.140T>C) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about RHAG p.Phe47Ser (c.140T>C)?

AlphaMissense predicts likely benign (score 0.0945) — an in-silico prediction, not a clinical call.

RHAG p.Phe47Ser

c.140T>C · rs2127360274 · VCV1322015

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0945 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0945	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.32	donor gain · deltas
Constraint at this position
Conservation	phyloP 1	GERP -3.5, phastCons 0.04
Regional constraint	o/e 0.96	unconstrained · MANE · 31 kb · p 0.34 · regional, not allelic
Overall
CADD	16.25	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,080 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000496% 8/1,613,926 alleles · very rare exomes 8/1,461,648 · genomes 0/152,278 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	8.48e-05%	1,179,802

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: RHAG
Protein: p.Phe47Ser
Coding: c.140T>C
MANE Select: NM_000324
dbSNP: rs2127360274
Type: single nucleotide variant
Location: chr6:49636673 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 8 PDB

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

Similar variants

RHAG c.157+1G>A Pathogenic/Likely pathogenic ★★ same type
RHAG p.Phe65Ser Pathogenic ★★ same type
RHAG c.341+4A>G Uncertain significance ★★ same type
RHAG p.Arg191Gln Uncertain significance ★★ ⚠ same type
RHAG p.Arg264Gln Uncertain significance ★★ ⚠ same type
RHAG p.Glu49Gln Uncertain significance ★★ ⚠ same type
RHAG p.His325Arg Uncertain significance ★★ ⚠ same type
RHAG p.Ile146Thr 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/rhag-p-phe47ser (accessed [today's date]).

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