Is ADAM11 p.Pro18Ser (c.52C>T) pathogenic?

ADAM11 p.Pro18Ser (c.52C>T) is classified Uncertain significance in ADAM11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.0999); Very rare (popmax 0.00156%, nfe).

How common is ADAM11 p.Pro18Ser (c.52C>T) in the general population?

ADAM11 p.Pro18Ser (c.52C>T) is very rare (popmax 0.00156%, nfe) (gnomAD).

What do computational predictors say about ADAM11 p.Pro18Ser (c.52C>T)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

ADAM11 p.Pro18Ser

c.52C>T · rs1231410947 · VCV3143928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00156%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -7.38	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 0.94	GERP 0.27, phastCons 0.43
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.068 · regional, not allelic
Overall
CADD	13.22	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 0.00156% European (non-Finnish) · 17/1,092,972 alleles

Filtering AF 0.000947% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000775%

Overall 0.00119% 17/1,431,692 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: ADAM11
Protein: p.Pro18Ser
Coding: c.52C>T
MANE Select: NM_002390
dbSNP: rs1231410947
Type: single nucleotide variant
Location: chr17:44759251 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.04

Full ADAM11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM11 p.Thr717Met Uncertain significance ★★ ⚠ same type
ADAM11 p.Ala147Thr Uncertain significance ★ ⚠ same type
ADAM11 p.Ala148Thr Uncertain significance ★ ⚠ same type
ADAM11 p.Ala214Ser Uncertain significance ★ ⚠ same type
ADAM11 p.Ala214Thr Uncertain significance ★ ⚠ same type
ADAM11 p.Ala326Thr Uncertain significance ★ ⚠ same type
ADAM11 p.Ala342Val Uncertain significance ★ ⚠ same type
ADAM11 p.Ala561Val 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/adam11-p-pro18ser (accessed [today's date]).

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