Is F11 p.Val38Phe (c.112G>T) pathogenic?

F11 p.Val38Phe (c.112G>T) is classified Uncertain significance in F11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-31). AlphaMissense: likely benign (0.1362); Very rare (popmax 0.00271%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F11 p.Val38Phe (c.112G>T)?

F11 p.Val38Phe (c.112G>T) is associated with Inborn genetic diseases (ClinVar).

How common is F11 p.Val38Phe (c.112G>T) in the general population?

F11 p.Val38Phe (c.112G>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about F11 p.Val38Phe (c.112G>T)?

AlphaMissense predicts likely benign (score 0.1362) — an in-silico prediction, not a clinical call.

F11 p.Val38Phe

c.112G>T · rs1165596644 · VCV3091386

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1362	likely benign
REVEL	0.568	indeterminate
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.31, phastCons 0.09
Overall
CADD	13.64	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 0.00271% European (non-Finnish) · 32/1,180,024 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00219% 32/1,461,876 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.Val38Phe
Coding: c.112G>T
MANE Select: NM_000128
dbSNP: rs1165596644
Type: single nucleotide variant
Location: chr4:186271665 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 38: a β-strand; the apple 1 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.Val38= Likely benign ★ 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.Ala316Gly Uncertain significance ★ ⚠ same condition
F11 p.Ala337Thr Uncertain significance ★ ⚠ same condition
F11 p.Ala570Thr Uncertain significance ★ ⚠ same condition
F11 p.Arg154Met 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-val38phe (accessed [today's date]).

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