Is ANKFN1 p.Ala93Val (c.278C>T) pathogenic?

ANKFN1 p.Ala93Val (c.278C>T) is classified Uncertain significance in ANKFN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely pathogenic (0.8915); Ultra-rare (popmax 0.0334%, eas).

How common is ANKFN1 p.Ala93Val (c.278C>T) in the general population?

ANKFN1 p.Ala93Val (c.278C>T) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

What do computational predictors say about ANKFN1 p.Ala93Val (c.278C>T)?

AlphaMissense predicts likely pathogenic (score 0.8915) — an in-silico prediction, not a clinical call.

ANKFN1 p.Ala93Val

c.278C>T · rs538479637 · VCV3120659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8915 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.8915	likely pathogenic
REVEL	0.216	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 299 kb · p 0.00097 · regional, not allelic
Overall
CADD	26.7	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 A96V vs ClinVar A93V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,852 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00112% 18/1,613,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,990
Remaining individualsnot grpmax-eligible	0.0048%	20,833

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.Ala93Val
Coding: c.278C>T
MANE Select: NM_001370326
dbSNP: rs538479637
Type: single nucleotide variant
Location: chr17:56350855 (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-ala93val (accessed [today's date]).

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