Is ANKRD13D p.Pro331Arg (c.992C>G) pathogenic?

ANKRD13D p.Pro331Arg (c.992C>G) is classified Uncertain significance in ANKRD13D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.2875); Absent from gnomAD v4.1.

How common is ANKRD13D p.Pro331Arg (c.992C>G) in the general population?

ANKRD13D p.Pro331Arg (c.992C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD13D p.Pro331Arg (c.992C>G)?

AlphaMissense predicts likely benign (score 0.2875) — an in-silico prediction, not a clinical call.

ANKRD13D p.Pro331Arg

c.992C>G · VCV4054980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2875 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2875	likely benign
REVEL	0.144	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 0.98
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.00076 · regional, not allelic
Overall
CADD	25.7	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P244R vs ClinVar P331R) — verify the residue.

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: ANKRD13D
Protein: p.Pro331Arg
Coding: c.992C>G
MANE Select: NM_207354
Type: single nucleotide variant
Location: chr11:67300042 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 73.38 · 1 PDB
Residue 331: the 'disordered' region

Full ANKRD13D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD13D p.Ala118Val Uncertain significance ★ ⚠ same type
ANKRD13D p.Ala223Val Uncertain significance ★ ⚠ same type
ANKRD13D p.Ala315Gly Uncertain significance ★ ⚠ same type
ANKRD13D p.Ala441Val Uncertain significance ★ ⚠ same type
ANKRD13D p.Ala498Gly Uncertain significance ★ same type
ANKRD13D p.Ala536Thr Uncertain significance ★ ⚠ same type
ANKRD13D p.Arg116His Uncertain significance ★ ⚠ same type
ANKRD13D p.Arg146Cys 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/ankrd13d-p-pro331arg (accessed [today's date]).

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