Is AR p.Ala766Ser (c.2296G>T) pathogenic?

AR p.Ala766Ser (c.2296G>T) is classified Likely pathogenic in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.7304); Absent from gnomAD v4.1; Associated with Differences in sex development.

What condition is associated with AR p.Ala766Ser (c.2296G>T)?

AR p.Ala766Ser (c.2296G>T) is associated with Differences in sex development (ClinVar).

How common is AR p.Ala766Ser (c.2296G>T) in the general population?

AR p.Ala766Ser (c.2296G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AR p.Ala766Ser (c.2296G>T)?

AlphaMissense predicts likely pathogenic (score 0.7304) — an in-silico prediction, not a clinical call.

AR p.Ala766Ser

c.2296G>T · VCV4281691

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7304 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Differences in sex development

Computational evidence

Protein change
AlphaMissense	0.7304	likely pathogenic ✓ concordant with ClinVar
REVEL	0.88	moderately pathogenic-leaning
SaProt	LLR -8.53	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 11	GERP 1.8, phastCons 1
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AR
Protein: p.Ala766Ser
Coding: c.2296G>T
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67717600 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 766: the nr lbd domain; the 'interaction with ccar1' region; the 'interaction with kat7' region; a UniProt-annotated variant site (in ais; loss of androgen binding); a UniProt-annotated variant site (in ais); a β-strand; the 'interaction with lpxn' region

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

Disease context

Differences in sex development

Similar variants

AR p.Ala766Thr Pathogenic ★★ same residue
AR p.Ala766Asp Pathogenic ★ same residue
AR p.Ala766Val Uncertain significance ★ ⚠ same residue
AR p.Ala597Thr Pathogenic ★★ same condition
AR p.Arg511Ter Pathogenic ★★ same condition
AR p.Arg608Gln Pathogenic/Likely pathogenic ★★ same condition
AR p.Arg753Gln Pathogenic/Likely pathogenic ★★ same condition
AR p.Arg841Cys Pathogenic ★★ 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-ala766ser (accessed [today's date]).

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