Is ADRM1 p.Met342Thr (c.1025T>C) pathogenic?

ADRM1 p.Met342Thr (c.1025T>C) is classified Uncertain significance in ADRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.6165); Very rare (popmax 0.00801%, afr).

How common is ADRM1 p.Met342Thr (c.1025T>C) in the general population?

ADRM1 p.Met342Thr (c.1025T>C) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about ADRM1 p.Met342Thr (c.1025T>C)?

AlphaMissense predicts likely pathogenic (score 0.6165) — an in-silico prediction, not a clinical call.

ADRM1 p.Met342Thr

c.1025T>C · VCV3502822

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6165 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6165	likely pathogenic
REVEL	0.353	indeterminate
SaProt	LLR -9.49	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 5,005 bp · p 0.0094 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.00801% African / African-American · 6/74,862 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000499% 8/1,603,618 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,477
European (non-Finnish)	0.00017%	588,412

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.Met342Thr
Coding: c.1025T>C
MANE Select: NM_007002
Type: single nucleotide variant
Location: chr20:62308378 (GRCh38)
Gene constraint: LOEUF 0.188 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.34 · 21 PDB
Residue 342: the deubad domain; an α-helix; the 'interaction with uchl5' region

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

Similar variants

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
ADRM1 p.Ala245Thr 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-met342thr (accessed [today's date]).

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