Is F3 p.Val62Ile (c.184G>A) pathogenic?

F3 p.Val62Ile (c.184G>A) is classified Likely benign in F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely benign (0.0618); Ultra-rare (popmax 0.0117%, amr).

How common is F3 p.Val62Ile (c.184G>A) in the general population?

F3 p.Val62Ile (c.184G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about F3 p.Val62Ile (c.184G>A)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

F3 p.Val62Ile

c.184G>A · VCV4020736

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.98	GERP -2.2
Overall
CADD	4.872	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 0.0117% Admixed American · 7/59,900 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000806% 13/1,613,082 alleles · ultra-rare exomes 10/1,460,968 · genomes 3/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,557
Remaining individualsnot grpmax-eligible	0.0016%	62,456
African / African-American	0.00134%	74,878
European (non-Finnish)	0.000339%	294,837

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.Val62Ile
Coding: c.184G>A
MANE Select: NM_001993
Type: single nucleotide variant
Location: chr1:94540285 (GRCh38)
Structure: AlphaFold pLDDT 87.29 · 2 PDB
Residue 62: 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.Ser62Ala Uncertain significance ★★ ⚠ same residue
CNTN1 p.Ser62Leu Uncertain significance ★ ⚠ same residue
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

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-val62ile (accessed [today's date]).

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