Is F3 p.Phe172Ser (c.515T>C) pathogenic?

F3 p.Phe172Ser (c.515T>C) is classified Uncertain significance in F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely pathogenic (0.5671); Absent from gnomAD v4.1.

How common is F3 p.Phe172Ser (c.515T>C) in the general population?

F3 p.Phe172Ser (c.515T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F3 p.Phe172Ser (c.515T>C)?

AlphaMissense predicts likely pathogenic (score 0.5671) — an in-silico prediction, not a clinical call.

F3 p.Phe172Ser

c.515T>C · rs2523642633 · VCV2638933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5671	likely pathogenic
REVEL	0.166	moderately benign-leaning
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.63 · regional, not allelic
Overall
CADD	23.3	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: F3
Protein: p.Phe172Ser
Coding: c.515T>C
MANE Select: NM_001993
dbSNP: rs2523642633
Type: single nucleotide variant
Location: chr1:94533166 (GRCh38)
Gene constraint: LOEUF 0.839 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40 · 54 PDB
Residue 172: a β-strand

Full F3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F3 p.Arg163Trp Benign ★★ ⚠ same type
F3 p.Gly281Glu Benign ★★ same type
F3 p.Thr36Ala Benign ★★ same type
F3 p.Ala17Thr Uncertain significance ★ ⚠ same type
F3 p.Ala30Thr Uncertain significance ★ ⚠ same type
F3 p.Arg11His Uncertain significance ★ ⚠ same type
F3 p.Arg176Trp Uncertain significance ★ same type
F3 p.Arg228Gln 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/f3-p-phe172ser (accessed [today's date]).

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