Is ANKRD53 p.Leu297Pro (c.890T>C) pathogenic?

ANKRD53 p.Leu297Pro (c.890T>C) is classified Uncertain significance in ANKRD53 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely pathogenic (0.8453); Absent from gnomAD v4.1.

How common is ANKRD53 p.Leu297Pro (c.890T>C) in the general population?

ANKRD53 p.Leu297Pro (c.890T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD53 p.Leu297Pro (c.890T>C)?

AlphaMissense predicts likely pathogenic (score 0.8453) — an in-silico prediction, not a clinical call.

ANKRD53 p.Leu297Pro

c.890T>C · VCV3399018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8453 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8453	likely pathogenic · top 4% in ANKRD53
REVEL	0.558	indeterminate
SaProt	LLR -11.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP 0.43, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 6,651 bp · p 0.15 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: ANKRD53
Protein: p.Leu297Pro
Coding: c.890T>C
MANE Select: NM_001115116
Type: single nucleotide variant
Location: chr2:70982684 (GRCh38)
Gene constraint: LOEUF 1.379 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41

Full ANKRD53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD53 p.Ala11Glu Uncertain significance ★ ⚠ same type
ANKRD53 p.Ala143Asp Uncertain significance ★ ⚠ same type
ANKRD53 p.Ala148Thr Uncertain significance ★ same type
ANKRD53 p.Ala219Ser Uncertain significance ★ ⚠ same type
ANKRD53 p.Ala242Thr Uncertain significance ★ ⚠ same type
ANKRD53 p.Ala310Thr Uncertain significance ★ ⚠ same type
ANKRD53 p.Ala39Pro Uncertain significance ★ ⚠ same type
ANKRD53 p.Ala434Pro 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/ankrd53-p-leu297pro (accessed [today's date]).

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