Is ADAM32 p.Leu7Pro (c.20T>C) pathogenic?

ADAM32 p.Leu7Pro (c.20T>C) is classified Uncertain significance in ADAM32 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.1704); Very rare (popmax 7.15e-05%).

How common is ADAM32 p.Leu7Pro (c.20T>C) in the general population?

ADAM32 p.Leu7Pro (c.20T>C) is very rare (popmax 7.15e-05%) (gnomAD).

What do computational predictors say about ADAM32 p.Leu7Pro (c.20T>C)?

AlphaMissense predicts likely benign (score 0.1704) — an in-silico prediction, not a clinical call.

ADAM32 p.Leu7Pro

c.20T>C · rs892274949 · VCV3145652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.15e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1704	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -13.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.06, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 177 kb · p 0.04 · regional, not allelic
Overall
CADD	21.3	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 7.15e-05%

Overall 7.15e-05% 1/1,398,078 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: ADAM32
Protein: p.Leu7Pro
Coding: c.20T>C
MANE Select: NM_145004
dbSNP: rs892274949
Type: single nucleotide variant
Location: chr8:39107795 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.71

Full ADAM32 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM32 p.Arg298His Likely benign ★★ ⚠ same type
ADAM32 p.Ala154Thr Uncertain significance ★ ⚠ same type
ADAM32 p.Ala179Ser Uncertain significance ★ ⚠ same type
ADAM32 p.Ala621Val Uncertain significance ★ ⚠ same type
ADAM32 p.Ala699Thr Uncertain significance ★ ⚠ same type
ADAM32 p.Arg284His Uncertain significance ★ ⚠ same type
ADAM32 p.Arg501Cys Uncertain significance ★ ⚠ same type
ADAM32 p.Arg501His 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/adam32-p-leu7pro (accessed [today's date]).

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