Is ANKIB1 p.Pro990Ala (c.2968C>G) pathogenic?

ANKIB1 p.Pro990Ala (c.2968C>G) is classified Uncertain significance in ANKIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0537); Very rare (popmax 0.00891%, eas).

How common is ANKIB1 p.Pro990Ala (c.2968C>G) in the general population?

ANKIB1 p.Pro990Ala (c.2968C>G) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about ANKIB1 p.Pro990Ala (c.2968C>G)?

AlphaMissense predicts likely benign (score 0.0537) — an in-silico prediction, not a clinical call.

ANKIB1 p.Pro990Ala

c.2968C>G · rs1187271425 · VCV3121125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0537 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0537	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 3.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,673 bp · p 0.17 · regional, not allelic
Overall
CADD	20.2	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 0.00891% East Asian · 4/44,882 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000372% 6/1,613,774 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
European (non-Finnish)	0.00017%	589,929

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.Pro990Ala
Coding: c.2968C>G
MANE Select: NM_019004
dbSNP: rs1187271425
Type: single nucleotide variant
Location: chr7:92398647 (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-pro990ala (accessed [today's date]).

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