Is ADRM1 p.Ser316Pro (c.946T>C) pathogenic?

ADRM1 p.Ser316Pro (c.946T>C) is classified Uncertain significance in ADRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely benign (0.1601); Very rare (popmax 8.48e-05%, nfe).

How common is ADRM1 p.Ser316Pro (c.946T>C) in the general population?

ADRM1 p.Ser316Pro (c.946T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ADRM1 p.Ser316Pro (c.946T>C)?

AlphaMissense predicts likely benign (score 0.1601) — an in-silico prediction, not a clinical call.

ADRM1 p.Ser316Pro

c.946T>C · VCV4020512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1601	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -3.84	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 6.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 5,005 bp · p 0.0094 · regional, not allelic
Overall
CADD	21.7	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 8.48e-05% European (non-Finnish) · 1/1,179,866 alleles

Overall 6.85e-05% 1/1,458,860 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: ADRM1
Protein: p.Ser316Pro
Coding: c.946T>C
MANE Select: NM_007002
Type: single nucleotide variant
Location: chr20:62308110 (GRCh38)
Gene constraint: LOEUF 0.188 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.34 · 21 PDB
Residue 316: the deubad domain; the 'interaction with uchl5' region

Full ADRM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADRM1 p.Ser316Cys Uncertain significance ★ ⚠ same residue
ADRM1 p.Ala245= Benign ★★ same type
ADRM1 p.Ala324Val Benign ★★ same type
ADRM1 p.Asp266= Benign ★★ same type
ADRM1 p.Pro315= Benign ★★ same type
ADRM1 p.Ala149Gly Uncertain significance ★ ⚠ same type
ADRM1 p.Ala236Thr Uncertain significance ★ ⚠ same type
ADRM1 p.Ala239Thr 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/adrm1-p-ser316pro (accessed [today's date]).

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