Is AR p.Asp605His (c.1813G>C) pathogenic?

AR p.Asp605His (c.1813G>C) is classified Likely pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-07). AlphaMissense: likely pathogenic (0.9999); Very rare (popmax 0.00175%, afr).

How common is AR p.Asp605His (c.1813G>C) in the general population?

AR p.Asp605His (c.1813G>C) is very rare (popmax 0.00175%, afr) (gnomAD).

What do computational predictors say about AR p.Asp605His (c.1813G>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

AR p.Asp605His

c.1813G>C · rs1266872442 · VCV451908

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 4% in AR
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -14.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	31.0	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 0.00175% African / African-American · 1/57,226 alleles

Overall 0.000891% 1/112,236 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: AR
Protein: p.Asp605His
Coding: c.1813G>C
MANE Select: NM_000044
dbSNP: rs1266872442
Type: single nucleotide variant
Location: chrX:67686054 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 605: the 'interaction with hipk3' region; the 'interaction with ccar1' region; a DNA-binding region; a UniProt-annotated variant site (in pais); the 'interaction with lpxn' region

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

Similar variants

AR p.Asp605Gly Pathogenic ★ same residue
AR p.Asp605= Benign ★ same residue
AR c.1768+2T>C Pathogenic/Likely pathogenic ★★ same type
AR c.1769-11T>A Pathogenic ★★ same type
AR c.2450-6C>G Pathogenic ★★ same type
AR p.Ala588Pro Pathogenic/Likely pathogenic ★★ same type
AR p.Ala597Thr Pathogenic ★★ same type
AR p.Ala688Val Pathogenic/Likely pathogenic ★★ 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/ar-p-asp605his (accessed [today's date]).

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