Is ADAM20 p.Gln537Arg (c.1610A>G) pathogenic?

ADAM20 p.Gln537Arg (c.1610A>G) is classified Uncertain significance in ADAM20 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely benign (0.0747); Very rare (popmax 0.00267%, afr).

How common is ADAM20 p.Gln537Arg (c.1610A>G) in the general population?

ADAM20 p.Gln537Arg (c.1610A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ADAM20 p.Gln537Arg (c.1610A>G)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

ADAM20 p.Gln537Arg

c.1610A>G · rs376740511 · VCV2487025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.79	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 -3	GERP -3.1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,177 bp · p 0.68 · regional, not allelic
Overall
CADD	13.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,018 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000205% 3/1,461,734 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,509
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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: ADAM20
Protein: p.Gln537Arg
Coding: c.1610A>G
MANE Select: NM_003814
dbSNP: rs376740511
Type: single nucleotide variant
Location: chr14:70523148 (GRCh38)
Gene constraint: LOEUF 1.933 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 83.06

Full ADAM20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM20 c.-117A>T Uncertain significance ★ same type
ADAM20 c.-125A>G Uncertain significance ★ same type
ADAM20 c.-63G>A Uncertain significance ★ same type
ADAM20 c.-71C>G Uncertain significance ★ same type
ADAM20 c.-77G>A Uncertain significance ★ same type
ADAM20 c.-90A>G Uncertain significance ★ same type
ADAM20 p.Ala124Pro Uncertain significance ★ ⚠ same type
ADAM20 p.Ala2Val 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/adam20-p-gln537arg (accessed [today's date]).

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