Is F11 p.Phe156Ser (c.467T>C) pathogenic?

F11 p.Phe156Ser (c.467T>C) is classified Uncertain significance in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.625); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with F11 p.Phe156Ser (c.467T>C)?

F11 p.Phe156Ser (c.467T>C) is associated with Inborn genetic diseases (ClinVar).

How common is F11 p.Phe156Ser (c.467T>C) in the general population?

F11 p.Phe156Ser (c.467T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about F11 p.Phe156Ser (c.467T>C)?

AlphaMissense predicts likely pathogenic (score 0.625) — an in-silico prediction, not a clinical call.

F11 p.Phe156Ser

c.467T>C · rs144674776 · VCV2491440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.625	likely pathogenic
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	23.8	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 0.00167% Admixed American · 1/60,002 alleles

Overall 0.000657% 1/152,194 alleles · very rare

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: F11
Protein: p.Phe156Ser
Coding: c.467T>C
MANE Select: NM_000128
dbSNP: rs144674776
Type: single nucleotide variant
Location: chr4:186274257 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 156: a disulfide bond; the apple 2 domain

Full F11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F11 p.Phe156Tyr Uncertain significance ★ ⚠ same residue
F11 p.Asp69Gly Uncertain significance ★★ ⚠ same condition
F11 p.Ile537Leu Uncertain significance ★★ ⚠ same condition
F11 p.Thr407Ala Uncertain significance ★★ ⚠ same condition
F11 p.Val38Phe Uncertain significance ★★ ⚠ same condition
F11 p.Ala316Gly Uncertain significance ★ ⚠ same condition
F11 p.Ala337Thr Uncertain significance ★ ⚠ same condition
F11 p.Ala570Thr Uncertain significance ★ ⚠ same condition

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/f11-p-phe156ser (accessed [today's date]).

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