Is ANKFY1 p.Ala305Pro (c.913G>C) pathogenic?

ANKFY1 p.Ala305Pro (c.913G>C) is classified Uncertain significance in ANKFY1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: likely pathogenic (0.9561); Ultra-rare (popmax 0.0346%, afr).

How common is ANKFY1 p.Ala305Pro (c.913G>C) in the general population?

ANKFY1 p.Ala305Pro (c.913G>C) is ultra-rare (popmax 0.0346%, afr) (gnomAD).

What do computational predictors say about ANKFY1 p.Ala305Pro (c.913G>C)?

AlphaMissense predicts likely pathogenic (score 0.9561) — an in-silico prediction, not a clinical call.

ANKFY1 p.Ala305Pro

c.913G>C · rs367611418 · VCV2252985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9561 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0346%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9561	likely pathogenic
REVEL	0.467	indeterminate
SaProt	LLR -12.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP -0.95, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 96 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0346% African / African-American · 26/75,044 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00173% 28/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0346%	2,886
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	8.47e-05%	1,180,008

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: ANKFY1
Protein: p.Ala305Pro
Coding: c.913G>C
MANE Select: NM_001330063
dbSNP: rs367611418
Type: single nucleotide variant
Location: chr17:4197563 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.98

Full ANKFY1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKFY1 p.Gly862Arg Uncertain significance ★★ ⚠ same type
ANKFY1 c.10+423G>A Benign ★★ same type
ANKFY1 c.11-31C>T Benign ★★ same type
ANKFY1 c.11-75A>G Benign ★★ same type
ANKFY1 c.1103+77G>A Benign ★★ same type
ANKFY1 c.1699+199G>A Benign ★★ same type
ANKFY1 c.1953-190G>T Benign ★★ same type
ANKFY1 c.2121+154C>T Benign ★★ 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/ankfy1-p-ala305pro (accessed [today's date]).

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