Is ANKRD26 p.Leu66Phe (c.196C>T) pathogenic?

ANKRD26 p.Leu66Phe (c.196C>T) is classified Uncertain significance in ANKRD26 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-05). AlphaMissense: likely pathogenic (0.7104); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ANKRD26 p.Leu66Phe (c.196C>T)?

ANKRD26 p.Leu66Phe (c.196C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANKRD26 p.Leu66Phe (c.196C>T) in the general population?

ANKRD26 p.Leu66Phe (c.196C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD26 p.Leu66Phe (c.196C>T)?

AlphaMissense predicts likely pathogenic (score 0.7104) — an in-silico prediction, not a clinical call.

ANKRD26 p.Leu66Phe

c.196C>T · VCV3340654

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7104 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7104	likely pathogenic · top 6% in ANKRD26
REVEL	0.203	benign-leaning
SaProt	LLR -10.07	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP 1.9
Regional constraint	o/e 1.00	unconstrained · MANE · 65 kb · p 0.96 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKRD26
Protein: p.Leu66Phe
Coding: c.196C>T
MANE Select: NM_014915
Type: single nucleotide variant
Location: chr10:27100131 (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.Leu66Val 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-leu66phe (accessed [today's date]).

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