Is ANKFN1 p.His32Pro (c.95A>C) pathogenic?

ANKFN1 p.His32Pro (c.95A>C) is classified Uncertain significance in ANKFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.094); Very rare (popmax 0.000339%, nfe).

How common is ANKFN1 p.His32Pro (c.95A>C) in the general population?

ANKFN1 p.His32Pro (c.95A>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about ANKFN1 p.His32Pro (c.95A>C)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

ANKFN1 p.His32Pro

c.95A>C · VCV4098602

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.065	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.69, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 299 kb · p 0.00097 · regional, not allelic
Overall
CADD	19.28	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM H35P vs ClinVar H32P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,876 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,600 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: ANKFN1
Protein: p.His32Pro
Coding: c.95A>C
MANE Select: NM_001370326
Type: single nucleotide variant
Location: chr17:56326262 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.55

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

Similar variants

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
ANKFN1 p.Ala361Thr 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-his32pro (accessed [today's date]).

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