Is ADAM29 p.Pro765= (c.2295C>T) pathogenic?

ADAM29 p.Pro765= (c.2295C>T) is classified Likely benign in ADAM29 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Rare (popmax 0.138%, amr).

How common is ADAM29 p.Pro765= (c.2295C>T) in the general population?

ADAM29 p.Pro765= (c.2295C>T) is rare (popmax 0.138%, amr) (gnomAD).

ADAM29 p.Pro765=

c.2295C>T · rs566589043 · VCV2655193

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.138%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	2.201	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.138% Admixed American · 77/55,760 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.09% 1,389/1,543,108 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.82%	21
Finnishnot grpmax-eligible	0.412%	243
Ashkenazi Jewishnot grpmax-eligible	0.143%	699
Admixed Americangrpmax	0.138%	724
Remaining individualsnot grpmax-eligible	0.128%	783
Middle Eastern	0.0879%	1,137
European (non-Finnish)	0.0763%	1,311
South Asian	0.0332%	3,015
African / African-American	0.0269%	3,715

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ADAM29
Protein: p.Pro765=
Coding: c.2295C>T
MANE Select: NM_014269
dbSNP: rs566589043
Type: single nucleotide variant
Location: chr4:174977820 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.07
Residue 765: the 'disordered' region; the '9 x 9 aa approximate repeats' region

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

Similar variants

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
ADAM29 p.Arg804Thr 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-pro765 (accessed [today's date]).

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