Is ADAM29 p.Arg724Pro (c.2171G>C) pathogenic?

ADAM29 p.Arg724Pro (c.2171G>C) is classified Likely benign in ADAM29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.0825); Absent from gnomAD v4.1.

How common is ADAM29 p.Arg724Pro (c.2171G>C) in the general population?

ADAM29 p.Arg724Pro (c.2171G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAM29 p.Arg724Pro (c.2171G>C)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

ADAM29 p.Arg724Pro

c.2171G>C · VCV4226423

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0825	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -5.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -1.6
Regional constraint	o/e 0.97	unconstrained · MANE · 2,459 bp · p 0.3 · regional, not allelic
Overall
CADD	0.038	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

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: ADAM29
Protein: p.Arg724Pro
Coding: c.2171G>C
MANE Select: NM_014269
Type: single nucleotide variant
Location: chr4:174977696 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.07
Residue 724: the 'disordered' region

Full ADAM29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM29 p.Arg724Gln Likely benign ★ same residue
ADAM29 p.Ala314Glu Uncertain significance ★ ⚠ same type
ADAM29 p.Ala88Val Uncertain significance ★ ⚠ same type
ADAM29 p.Arg213Cys Uncertain significance ★ ⚠ same type
ADAM29 p.Arg311His Uncertain significance ★ ⚠ same type
ADAM29 p.Arg501His Uncertain significance ★ ⚠ same type
ADAM29 p.Arg530Cys Uncertain significance ★ ⚠ same type
ADAM29 p.Arg723Cys 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/adam29-p-arg724pro (accessed [today's date]).

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