Is F11 p.Glu245Val (c.734A>T) pathogenic?

F11 p.Glu245Val (c.734A>T) is classified Uncertain significance in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1631); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with F11 p.Glu245Val (c.734A>T)?

F11 p.Glu245Val (c.734A>T) is associated with Inborn genetic diseases (ClinVar).

How common is F11 p.Glu245Val (c.734A>T) in the general population?

F11 p.Glu245Val (c.734A>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about F11 p.Glu245Val (c.734A>T)?

AlphaMissense predicts likely benign (score 0.1631) — an in-silico prediction, not a clinical call.

F11 p.Glu245Val

c.734A>T · rs995963085 · VCV2485010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1631 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1631	likely benign
REVEL	0.463	indeterminate
SaProt	LLR -9.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.07 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.3	GERP -1.4, phastCons 0.015
Overall
CADD	16.81	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 0.0011% South Asian · 1/91,076 alleles

Overall 6.84e-05% 1/1,461,876 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.Glu245Val
Coding: c.734A>T
MANE Select: NM_000128
dbSNP: rs995963085
Type: single nucleotide variant
Location: chr4:186276369 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 245: a disulfide bond; the apple 3 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.Glu245Gly 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-glu245val (accessed [today's date]).

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