Is ANKIB1 p.Ser95Phe (c.284C>T) pathogenic?

ANKIB1 p.Ser95Phe (c.284C>T) is classified Uncertain significance in ANKIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.275); Ultra-rare (popmax 0.0667%, amr).

How common is ANKIB1 p.Ser95Phe (c.284C>T) in the general population?

ANKIB1 p.Ser95Phe (c.284C>T) is ultra-rare (popmax 0.0667%, amr) (gnomAD).

What do computational predictors say about ANKIB1 p.Ser95Phe (c.284C>T)?

AlphaMissense predicts likely benign (score 0.275) — an in-silico prediction, not a clinical call.

ANKIB1 p.Ser95Phe

c.284C>T · VCV3865398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.275 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.275	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 3.4, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 56 bp · p 0.29 · regional, not allelic
Overall
CADD	27.5	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 0.0667% Admixed American · 40/60,002 alleles

Filtering AF 0.0503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0446%

Overall 0.00254% 41/1,613,814 alleles · ultra-rare exomes 39/1,461,680 · genomes 2/152,134 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0667%	1,500
European (non-Finnish)	8.48e-05%	1,179,880

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: ANKIB1
Protein: p.Ser95Phe
Coding: c.284C>T
MANE Select: NM_019004
Type: single nucleotide variant
Location: chr7:92307454 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 66.52

Full ANKIB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKIB1 c.-605T>C Benign/Likely benign ★★ same type
ANKIB1 p.Ala1062Val Uncertain significance ★ ⚠ same type
ANKIB1 p.Ala126Thr Uncertain significance ★ ⚠ same type
ANKIB1 p.Ala218Thr Uncertain significance ★ ⚠ same type
ANKIB1 p.Ala257Gly Uncertain significance ★ ⚠ same type
ANKIB1 p.Ala986Val Uncertain significance ★ ⚠ same type
ANKIB1 p.Arg102Cys Uncertain significance ★ same type
ANKIB1 p.Arg102Leu 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/ankib1-p-ser95phe (accessed [today's date]).

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