Is ADAM11 p.Ser337Arg (c.1011C>G) pathogenic?

ADAM11 p.Ser337Arg (c.1011C>G) is classified Uncertain significance in ADAM11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.6678); Absent from gnomAD v4.1.

How common is ADAM11 p.Ser337Arg (c.1011C>G) in the general population?

ADAM11 p.Ser337Arg (c.1011C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAM11 p.Ser337Arg (c.1011C>G)?

AlphaMissense predicts likely pathogenic (score 0.6678) — an in-silico prediction, not a clinical call.

ADAM11 p.Ser337Arg

c.1011C>G · VCV4003997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6678 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,472,120)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6678	likely pathogenic
REVEL	0.224	benign-leaning
SaProt	LLR -8.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -0.7, phastCons 0.99
Regional constraint	o/e 0.66	unconstrained · MANE · 1,840 bp · p 3.3e-07 · regional, not allelic
Overall
CADD	23.4	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

No allele count reported in gnomAD v4.1 (AN 1,472,120). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADAM11
Protein: p.Ser337Arg
Coding: c.1011C>G
MANE Select: NM_002390
Type: single nucleotide variant
Location: chr17:44774313 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.04
Residue 337: the 'required for localization to cerebellar cortex basket cell terminals. also required for localization of kcna1, kcna2, dlg4 and adam22 to cerebellar cortex basket cell terminal perisomatic axons and pinceaux' region; the peptidase m12b domain

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-ser337arg (accessed [today's date]).

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