Is ANKRD29 p.Arg36Trp (c.106C>T) pathogenic?

ANKRD29 p.Arg36Trp (c.106C>T) is classified Uncertain significance in ANKRD29 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: ambiguous (0.3527); Ultra-rare (popmax 0.01%, nfe).

How common is ANKRD29 p.Arg36Trp (c.106C>T) in the general population?

ANKRD29 p.Arg36Trp (c.106C>T) is ultra-rare (popmax 0.01%, nfe) (gnomAD).

What do computational predictors say about ANKRD29 p.Arg36Trp (c.106C>T)?

AlphaMissense predicts ambiguous (score 0.3527) — an in-silico prediction, not a clinical call.

ANKRD29 p.Arg36Trp

c.106C>T · VCV3297043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3527 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3527	ambiguous
REVEL	0.359	indeterminate
SaProt	LLR -8.39	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 62 kb · p 0.28 · regional, not allelic
Overall
CADD	33.0	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 0.01% European (non-Finnish) · 118/1,179,988 alleles

Filtering AF 0.00851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00795%

Overall 0.00805% 130/1,613,950 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.0096%	10,413
Admixed American	0.00834%	11,997
African / African-American	0.00133%	74,916

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: ANKRD29
Protein: p.Arg36Trp
Coding: c.106C>T
MANE Select: NM_173505
Type: single nucleotide variant
Location: chr18:23649109 (GRCh38)
Gene constraint: LOEUF 1.187 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.86

Full ANKRD29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD29 p.Arg36Gln Uncertain significance ★ ⚠ same residue
ANKRD29 p.Ala103Thr Uncertain significance ★ same type
ANKRD29 p.Ala185Pro Uncertain significance ★ ⚠ same type
ANKRD29 p.Ala202Val Uncertain significance ★ same type
ANKRD29 p.Ala249Val Uncertain significance ★ ⚠ same type
ANKRD29 p.Ala260Val Uncertain significance ★ ⚠ same type
ANKRD29 p.Ala280Thr Uncertain significance ★ ⚠ same type
ANKRD29 p.Ala280Val 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/ankrd29-p-arg36trp (accessed [today's date]).

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