Is ANKRD23 p.Ser276Pro (c.826T>C) pathogenic?

ANKRD23 p.Ser276Pro (c.826T>C) is classified Uncertain significance in ANKRD23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely pathogenic (0.585); Very rare (popmax 0.00233%, eas).

How common is ANKRD23 p.Ser276Pro (c.826T>C) in the general population?

ANKRD23 p.Ser276Pro (c.826T>C) is very rare (popmax 0.00233%, eas) (gnomAD).

What do computational predictors say about ANKRD23 p.Ser276Pro (c.826T>C)?

AlphaMissense predicts likely pathogenic (score 0.585) — an in-silico prediction, not a clinical call.

ANKRD23 p.Ser276Pro

c.826T>C · VCV3296701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.585 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00233%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.585	likely pathogenic
REVEL	0.206	benign-leaning
SaProt	LLR -11.44	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 6.3	GERP 0.73, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 4,440 bp · p 0.43 · regional, not allelic
Overall
CADD	23.1	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 0.00233% East Asian · 1/42,980 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000198% 3/1,518,262 alleles · very rare exomes 2/1,366,068 · genomes 1/152,194 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00233%	42,980
European (non-Finnish)	0.000177%	565,524

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: ANKRD23
Protein: p.Ser276Pro
Coding: c.826T>C
MANE Select: NM_144994
Type: single nucleotide variant
Location: chr2:96839641 (GRCh38)
Gene constraint: LOEUF 1.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.08

Full ANKRD23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD23 p.Ala166Ser Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala172Thr Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala172Val Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala238Thr Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala43Val Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala73Gly Uncertain significance ★ ⚠ same type
ANKRD23 p.Ala73Pro Uncertain significance ★ ⚠ same type
ANKRD23 p.Arg145Cys 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/ankrd23-p-ser276pro (accessed [today's date]).

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