Is ANKRD13D p.Arg596Trp (c.1786C>T) pathogenic?

ANKRD13D p.Arg596Trp (c.1786C>T) is classified Uncertain significance in ANKRD13D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.2042); Very rare (popmax 8.72e-05%, nfe).

How common is ANKRD13D p.Arg596Trp (c.1786C>T) in the general population?

ANKRD13D p.Arg596Trp (c.1786C>T) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about ANKRD13D p.Arg596Trp (c.1786C>T)?

AlphaMissense predicts likely benign (score 0.2042) — an in-silico prediction, not a clinical call.

ANKRD13D p.Arg596Trp

c.1786C>T · VCV4101483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2042	likely benign
REVEL	0.163	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 1.6	GERP -1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.00076 · regional, not allelic
Overall
CADD	25.6	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 R509W vs ClinVar R596W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,298 alleles

Overall 0.000657% 1/152,196 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: ANKRD13D
Protein: p.Arg596Trp
Coding: c.1786C>T
MANE Select: NM_207354
Type: single nucleotide variant
Location: chr11:67302300 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 73.38 · 1 PDB
Residue 596: an α-helix; the uim 4 domain; the 'disordered' region

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

Similar variants

ANKRD13D p.Arg596Gln Uncertain significance ★ ⚠ same residue
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

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-arg596trp (accessed [today's date]).

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