Is ANKIB1 p.Arg102Leu (c.305G>T) pathogenic?

ANKIB1 p.Arg102Leu (c.305G>T) is classified Uncertain significance in ANKIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely pathogenic (0.6352); Ultra-rare (popmax 0.0164%, mid).

How common is ANKIB1 p.Arg102Leu (c.305G>T) in the general population?

ANKIB1 p.Arg102Leu (c.305G>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ANKIB1 p.Arg102Leu (c.305G>T)?

AlphaMissense predicts likely pathogenic (score 0.6352) — an in-silico prediction, not a clinical call.

ANKIB1 p.Arg102Leu

c.305G>T · VCV3865427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6352 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6352	likely pathogenic
REVEL	0.442	indeterminate
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.4, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 56 bp · p 0.29 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,676 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.0011%	91,080
European (non-Finnish)	0.000678%	147,484

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.Arg102Leu
Coding: c.305G>T
MANE Select: NM_019004
Type: single nucleotide variant
Location: chr7:92307475 (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 p.Arg102Cys Uncertain significance ★ ⚠ same residue
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.Arg105Cys 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-arg102leu (accessed [today's date]).

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