Is ANKRD26 p.Leu167Phe (c.501G>T) pathogenic?

ANKRD26 p.Leu167Phe (c.501G>T) is classified Conflicting classifications of pathogenicity in ANKRD26 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-31). AlphaMissense: likely benign (0.0998); Rare (popmax 0.143%, amr); Associated with Inborn genetic diseases.

What condition is associated with ANKRD26 p.Leu167Phe (c.501G>T)?

ANKRD26 p.Leu167Phe (c.501G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD26 p.Leu167Phe (c.501G>T) in the general population?

ANKRD26 p.Leu167Phe (c.501G>T) is rare (popmax 0.143%, amr) (gnomAD).

What do computational predictors say about ANKRD26 p.Leu167Phe (c.501G>T)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

ANKRD26 p.Leu167Phe

c.501G>T · rs183398279 · VCV1314106

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.143%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -7.09	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 -14	GERP -3.7
Regional constraint	o/e 1.00	unconstrained · MANE · 65 kb · p 0.96 · regional, not allelic
Overall
CADD	0.1	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 0.143% Admixed American · 86/60,010 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.00539% 87/1,614,094 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.143%	698
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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: ANKRD26
Protein: p.Leu167Phe
Coding: c.501G>T
MANE Select: NM_014915
dbSNP: rs183398279
Type: single nucleotide variant
Location: chr10:27093379 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.91

Full ANKRD26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANKRD26 p.Leu167Trp Uncertain significance ★ ⚠ same residue
ANKRD26 p.Ala1014Ser Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1015Val Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala120Thr Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1215Thr Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1284Ser Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1416Val Uncertain significance ★★ ⚠ same condition
ANKRD26 p.Ala1503Ser Uncertain significance ★★ ⚠ same condition

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/ankrd26-p-leu167phe (accessed [today's date]).

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