Is F3 p.Thr85Ile (c.254C>T) pathogenic?

F3 p.Thr85Ile (c.254C>T) is classified Uncertain significance in F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely benign (0.2595); Very rare (popmax 0.00666%, amr).

How common is F3 p.Thr85Ile (c.254C>T) in the general population?

F3 p.Thr85Ile (c.254C>T) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about F3 p.Thr85Ile (c.254C>T)?

AlphaMissense predicts likely benign (score 0.2595) — an in-silico prediction, not a clinical call.

F3 p.Thr85Ile

c.254C>T · VCV3511280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2595 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2595	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -9.64	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 0.33	GERP 1.6
Overall
CADD	19.2	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 0.00666% Admixed American · 4/60,034 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000274% 4/1,461,878 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: F3
Protein: p.Thr85Ile
Coding: c.254C>T
MANE Select: NM_001843 · reported on NM_001993
Type: single nucleotide variant
Location: chr1:94536123 (GRCh38)
Structure: AlphaFold pLDDT 87.29 · 2 PDB
Residue 85: a disulfide bond; the ig-like c2-type 1 domain

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

Similar variants

CNTN1 p.Ala410Val Uncertain significance ★★ ⚠ same type
CNTN1 p.Ala514Thr Uncertain significance ★★ ⚠ same type
CNTN1 p.Ala528Val Uncertain significance ★★ ⚠ same type
CNTN1 p.Ala668Thr Uncertain significance ★★ ⚠ same type
CNTN1 p.Ala799Thr Uncertain significance ★★ ⚠ same type
CNTN1 p.Ala930Ser Uncertain significance ★★ ⚠ same type
CNTN1 p.Ala995Thr Uncertain significance ★★ ⚠ same type
CNTN1 p.Arg274Gln 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-thr85ile (accessed [today's date]).

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