Is ADAMTS7 p.Pro1435= (c.4305G>A) pathogenic?

ADAMTS7 p.Pro1435= (c.4305G>A) is classified Likely benign in ADAMTS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Ultra-rare (popmax 0.0407%, eas).

How common is ADAMTS7 p.Pro1435= (c.4305G>A) in the general population?

ADAMTS7 p.Pro1435= (c.4305G>A) is ultra-rare (popmax 0.0407%, eas) (gnomAD).

ADAMTS7 p.Pro1435=

c.4305G>A · rs368083728 · VCV2645616

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0407%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.4
Overall
CADD	0.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0407% East Asian · 18/44,280 alleles

Filtering AF 0.0266% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0225%

Overall 0.0111% 175/1,570,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.102%	981
East Asiangrpmax	0.0407%	2,460
Admixed American	0.0395%	2,534
European (non-Finnish)	0.00591%	16,914
South Asian	0.00346%	28,883
African / African-American	0.00135%	74,022

Remaining individuals 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: ADAMTS7
Protein: p.Pro1435=
Coding: c.4305G>A
MANE Select: NM_014272
dbSNP: rs368083728
Type: single nucleotide variant
Location: chr15:78764669 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.26
Residue 1435: the tsp type-1 5 domain

Full ADAMTS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAMTS7 p.Arg218His Likely benign ★★ ⚠ same type
ADAMTS7 p.Cys1553= Benign/Likely benign ★★ same type
ADAMTS7 p.Pro568= Benign ★★ same type
ADAMTS7 p.Ser237= Likely benign ★★ same type
ADAMTS7 p.Thr307Met Benign ★★ ⚠ same type
ADAMTS7 p.Ala1019Thr Uncertain significance ★ ⚠ same type
ADAMTS7 p.Ala1049Thr Uncertain significance ★ ⚠ same type
ADAMTS7 p.Ala1166Thr 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/adamts7-p-pro1435 (accessed [today's date]).

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