Is AR p.Asp691Asn (c.2071G>A) pathogenic?

AR p.Asp691Asn (c.2071G>A) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely pathogenic (0.7507); Very rare (popmax 0.00296%, eas); Associated with Inborn genetic diseases.

What condition is associated with AR p.Asp691Asn (c.2071G>A)?

AR p.Asp691Asn (c.2071G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AR p.Asp691Asn (c.2071G>A) in the general population?

AR p.Asp691Asn (c.2071G>A) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about AR p.Asp691Asn (c.2071G>A)?

AlphaMissense predicts likely pathogenic (score 0.7507) — an in-silico prediction, not a clinical call.

AR p.Asp691Asn

c.2071G>A · VCV4583434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7507 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7507	likely pathogenic
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -9.29	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	27.8	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 0.00296% East Asian · 1/33,732 alleles

Filtering AF 0.00136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00182% 22/1,209,766 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,732
Admixed American	0.00219%	45,751
European (non-Finnish)	0.00212%	47,114
Remaining individualsnot grpmax-eligible	0.0021%	47,591

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: AR
Protein: p.Asp691Asn
Coding: c.2071G>A
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67711587 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 691: the nr lbd domain; the 'interaction with ccar1' region; a UniProt-annotated variant site (in pais); the 'interaction with kat7' region; the 'interaction with lpxn' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AR p.Asp691Glu Pathogenic ★ same residue
AR p.Asp691Gly Likely pathogenic ★ same residue
AR p.Asp691= Benign ★ same residue
AR p.Leu446Trp Uncertain significance ★★ ⚠ same condition
AR p.Gly471= Likely benign ★★ same condition
AR p.Ala151Glu Uncertain significance ★ ⚠ same condition
AR p.Ala253Gly Uncertain significance ★ ⚠ same condition
AR p.Ala331Asp Uncertain significance ★ ⚠ same condition

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/ar-p-asp691asn (accessed [today's date]).

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