Is ADAM23 p.Ala37Val (c.110C>T) pathogenic?

ADAM23 p.Ala37Val (c.110C>T) is classified Uncertain significance in ADAM23 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.1071); Rare (popmax 0.114%, nfe).

How common is ADAM23 p.Ala37Val (c.110C>T) in the general population?

ADAM23 p.Ala37Val (c.110C>T) is rare (popmax 0.114%, nfe) (gnomAD).

What do computational predictors say about ADAM23 p.Ala37Val (c.110C>T)?

AlphaMissense predicts likely benign (score 0.1071) — an in-silico prediction, not a clinical call.

ADAM23 p.Ala37Val

c.110C>T · rs756280188 · VCV2353139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1071 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1071	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.19	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 0.79	GERP -2, phastCons 0.99
Regional constraint	o/e 1.10	unconstrained · MANE · 37 kb · p 0.14 · regional, not allelic
Overall
CADD	15.65	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 0.114% European (non-Finnish) · 1,210/1,057,608 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.0923% 1,264/1,369,442 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.114%	874
Remaining individualsnot grpmax-eligible	0.0587%	1,703
African / African-American	0.021%	4,770
Finnishnot grpmax-eligible	0.013%	7,694
Admixed American	0.0109%	9,135
South Asian	0.0017%	58,858

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: ADAM23
Protein: p.Ala37Val
Coding: c.110C>T
MANE Select: NM_003812
dbSNP: rs756280188
Type: single nucleotide variant
Location: chr2:206443976 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.38
Residue 37: the 'disordered' region

Full ADAM23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM23 p.Ile118Met Likely benign ★★ ⚠ same type
ADAM23 p.Phe158= Likely benign ★★ same type
ADAM23 p.Pro780Ala Benign/Likely benign ★★ same type
ADAM23 p.Ser125Ala Likely benign ★★ same type
ADAM23 p.Ser693= Benign ★★ same type
ADAM23 c.1346-1G>C Uncertain significance ★ same type
ADAM23 p.Ala145Gly Uncertain significance ★ ⚠ same type
ADAM23 p.Ala287Thr 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/adam23-p-ala37val (accessed [today's date]).

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