Is ADRM1 p.Asp53Glu (c.159C>G) pathogenic?

ADRM1 p.Asp53Glu (c.159C>G) is classified Benign in ADRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-04). AlphaMissense: likely benign (0.1844); Rare (popmax 0.956%, afr).

How common is ADRM1 p.Asp53Glu (c.159C>G) in the general population?

ADRM1 p.Asp53Glu (c.159C>G) is rare (popmax 0.956%, afr) (gnomAD).

What do computational predictors say about ADRM1 p.Asp53Glu (c.159C>G)?

AlphaMissense predicts likely benign (score 0.1844) — an in-silico prediction, not a clinical call.

ADRM1 p.Asp53Glu

c.159C>G · rs115562292 · VCV722428

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1844 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.956%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1844	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.79	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 -2	GERP -2.2
Regional constraint	o/e 0.33	constrained · MANE · 113 bp · p 2.3e-06 · regional, not allelic
Overall
CADD	17.96	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 0.956% African / African-American · 717/75,036 alleles

Filtering AF 0.898% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.874%

Overall 0.0501% 807/1,612,366 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.956%	105
Remaining individualsnot grpmax-eligible	0.0784%	1,275
Admixed American	0.055%	1,819
Middle Eastern	0.033%	3,030
South Asian	0.0022%	45,538
European (non-Finnish)	0.000339%	294,994

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.Asp53Glu
Coding: c.159C>G
MANE Select: NM_007002
dbSNP: rs115562292
Type: single nucleotide variant
Location: chr20:62303727 (GRCh38)
Gene constraint: LOEUF 0.188 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.34 · 21 PDB
Residue 53: the pru domain

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-asp53glu (accessed [today's date]).

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