Is ANKRD12 p.Ser1243Pro (c.3727T>C) pathogenic?

ANKRD12 p.Ser1243Pro (c.3727T>C) is classified Uncertain significance in ANKRD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely benign (0.0775); Very rare (popmax 0.00805%, nfe).

How common is ANKRD12 p.Ser1243Pro (c.3727T>C) in the general population?

ANKRD12 p.Ser1243Pro (c.3727T>C) is very rare (popmax 0.00805%, nfe) (gnomAD).

What do computational predictors say about ANKRD12 p.Ser1243Pro (c.3727T>C)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

ANKRD12 p.Ser1243Pro

c.3727T>C · VCV3543948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00805%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 37 kb · p 6.1e-10 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00805% European (non-Finnish) · 95/1,180,006 alleles

Filtering AF 0.00672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00624%

Overall 0.00589% 95/1,614,010 alleles · very rare

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: ANKRD12
Protein: p.Ser1243Pro
Coding: c.3727T>C
MANE Select: NM_015208
Type: single nucleotide variant
Location: chr18:9256994 (GRCh38)
Gene constraint: LOEUF 0.583 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 41.33

Full ANKRD12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD12 p.Ala1049Thr Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1393Val Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1479Val Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1572Val Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1752Gly Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1805Thr Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala1814Glu Uncertain significance ★ ⚠ same type
ANKRD12 p.Ala2013Val 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/ankrd12-p-ser1243pro (accessed [today's date]).

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