Is ANKFN1 p.Val342Phe (c.1024G>T) pathogenic?

ANKFN1 p.Val342Phe (c.1024G>T) is classified Uncertain significance in ANKFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: ambiguous (0.5066); Absent from gnomAD v4.1.

How common is ANKFN1 p.Val342Phe (c.1024G>T) in the general population?

ANKFN1 p.Val342Phe (c.1024G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKFN1 p.Val342Phe (c.1024G>T)?

AlphaMissense predicts ambiguous (score 0.5066) — an in-silico prediction, not a clinical call.

ANKFN1 p.Val342Phe

c.1024G>T · VCV3865175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5066 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5066	ambiguous
REVEL	0.183	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 299 kb · p 0.00097 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V345F vs ClinVar V342F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKFN1
Protein: p.Val342Phe
Coding: c.1024G>T
MANE Select: NM_001370326
Type: single nucleotide variant
Location: chr17:56442858 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.55
Residue 342: the fibronectin type-iii domain

Full ANKFN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKFN1 p.Val342Ile Uncertain significance ★ ⚠ same residue
ANKFN1 c.2260+19C>T Uncertain significance ★ ⚠ same type
ANKFN1 c.-73A>G Uncertain significance ★ ⚠ same type
ANKFN1 c.-88G>C Uncertain significance ★ ⚠ same type
ANKFN1 p.Ala24Thr Uncertain significance ★ ⚠ same type
ANKFN1 p.Ala267Val Uncertain significance ★ ⚠ same type
ANKFN1 p.Ala346Ser Uncertain significance ★ same type
ANKFN1 p.Ala361Glu 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/ankfn1-p-val342phe (accessed [today's date]).

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