Is ANKRD26 p.Pro38Ser (c.112C>T) pathogenic?

ANKRD26 p.Pro38Ser (c.112C>T) is classified Conflicting classifications of pathogenicity in ANKRD26 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.1322); Ultra-rare (popmax 0.0117%, amr); Associated with ANKRD26-related disorder.

What condition is associated with ANKRD26 p.Pro38Ser (c.112C>T)?

ANKRD26 p.Pro38Ser (c.112C>T) is associated with ANKRD26-related disorder (ClinVar).

How common is ANKRD26 p.Pro38Ser (c.112C>T) in the general population?

ANKRD26 p.Pro38Ser (c.112C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about ANKRD26 p.Pro38Ser (c.112C>T)?

AlphaMissense predicts likely benign (score 0.1322) — an in-silico prediction, not a clinical call.

ANKRD26 p.Pro38Ser

c.112C>T · rs374871257 · VCV450395

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1322 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ANKRD26-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1322	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6.6	GERP -1
Regional constraint	o/e 1.00	unconstrained · MANE · 65 kb · p 0.96 · regional, not allelic
Overall
CADD	7.924	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 0.0117% Admixed American · 7/60,008 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00434% 70/1,613,170 alleles · ultra-rare exomes 67/1,460,926 · genomes 3/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
European (non-Finnish)	0.00525%	19,030
Finnishnot grpmax-eligible	0.00158%	63,324

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.Pro38Ser
Coding: c.112C>T
MANE Select: NM_014915
dbSNP: rs374871257
Type: single nucleotide variant
Location: chr10:27100215 (GRCh38)

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

Disease context

ANKRD26-related disorder

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-pro38ser (accessed [today's date]).

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