Is F3 p.Ala30Thr (c.88G>A) pathogenic?

F3 p.Ala30Thr (c.88G>A) is classified Uncertain significance in F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.1073); Ultra-rare (popmax 0.02%, amr).

How common is F3 p.Ala30Thr (c.88G>A) in the general population?

F3 p.Ala30Thr (c.88G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about F3 p.Ala30Thr (c.88G>A)?

AlphaMissense predicts likely benign (score 0.1073) — an in-silico prediction, not a clinical call.

F3 p.Ala30Thr

c.88G>A · rs768720096 · VCV3091455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1073	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.72	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 -1.9, phastCons 0.001
Overall
CADD	13.06	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 0.02% Admixed American · 9/44,940 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00778%

Overall 0.0018% 27/1,497,746 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,993
Remaining individualsnot grpmax-eligible	0.007%	14,278
African / African-American	0.00287%	34,787
European (non-Finnish)	0.00107%	93,734

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.Ala30Thr
Coding: c.88G>A
MANE Select: NM_001843 · reported on NM_001993
dbSNP: rs768720096
Type: single nucleotide variant
Location: chr1:94541549 (GRCh38)
Structure: AlphaFold pLDDT 87.29 · 2 PDB

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

Similar variants

CNTN1 p.His30= Benign ★★ 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
CNTN1 p.Ala995Thr 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-ala30thr (accessed [today's date]).

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