Is F2R p.Ser275Phe (c.824C>T) pathogenic?

F2R p.Ser275Phe (c.824C>T) is classified Uncertain significance in F2R (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-12). AlphaMissense: likely pathogenic (0.7288); Very rare (popmax 0.004%, afr).

How common is F2R p.Ser275Phe (c.824C>T) in the general population?

F2R p.Ser275Phe (c.824C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about F2R p.Ser275Phe (c.824C>T)?

AlphaMissense predicts likely pathogenic (score 0.7288) — an in-silico prediction, not a clinical call.

F2R p.Ser275Phe

c.824C>T · VCV4252311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7288	likely pathogenic
REVEL	0.555	indeterminate
SaProt	LLR -9.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 0.97
Regional constraint	o/e 0.83	unconstrained · MANE · 17 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	23.6	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

Grpmax group 0.004% African / African-American · 3/74,924 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000558% 9/1,614,066 alleles · very rare exomes 6/1,461,870 · genomes 3/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,975
European (non-Finnish)	0.000508%	196,674

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: F2R
Protein: p.Ser275Phe
Coding: c.824C>T
MANE Select: NM_001992
Type: single nucleotide variant
Location: chr5:76733049 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 13 PDB
Residue 275: an α-helix

Full F2R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F2R p.Ser275Cys Uncertain significance ★ ⚠ same residue
F2R p.Leu38= Benign ★★ same type
F2R p.Ser172= Benign ★★ same type
F2R p.Tyr381Cys Benign ★★ same type
F2R p.Val246= Benign ★★ same type
F2R p.Ala10Val Uncertain significance ★ ⚠ same type
F2R p.Ala203Thr Uncertain significance ★ ⚠ same type
F2R p.Ala268Ser 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/f2r-p-ser275phe (accessed [today's date]).

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