Is AR p.Pro392Ser (c.1174C>T) pathogenic?

AR p.Pro392Ser (c.1174C>T) is classified Conflicting classifications of pathogenicity in AR (ClinVar, Conflicting submitters, 16 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0686); Low-frequency (popmax 2.49%, sas); Associated with partial androgen insensitivity syndrome.

What condition is associated with AR p.Pro392Ser (c.1174C>T)?

AR p.Pro392Ser (c.1174C>T) is associated with partial androgen insensitivity syndrome, hypospadias 1, X-linked, Kennedy disease (ClinVar).

How common is AR p.Pro392Ser (c.1174C>T) in the general population?

AR p.Pro392Ser (c.1174C>T) is low-frequency (popmax 2.49%, sas) (gnomAD).

How is Partial androgen insensitivity syndrome inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AR p.Pro392Ser (c.1174C>T)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

AR p.Pro392Ser

c.1174C>T · rs201934623 · VCV216890

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.49%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

partial androgen insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.766	pathogenic-leaning
SaProt	LLR -6.31	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.34, phastCons 1
Overall
CADD	16.38	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 2.49% South Asian · 1,377/55,219 alleles

Filtering AF 2.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.34%

Overall 0.324% 3,878/1,197,127 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.49%	40
Middle Eastern	0.957%	104
Remaining individualsnot grpmax-eligible	0.344%	290
European (non-Finnish)	0.239%	418
Ashkenazi Jewishnot grpmax-eligible	0.234%	427
Admixed American	0.193%	517
Finnishnot grpmax-eligible	0.0316%	3,160
African / African-American	0.0279%	3,580
East Asian	0.00605%	16,523

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.Pro392Ser
Coding: c.1174C>T
MANE Select: NM_000044
dbSNP: rs201934623
Type: single nucleotide variant
Location: chrX:67546320 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 392: the 'interaction with znf318' region; a UniProt-annotated variant site (in ais); the 'modulating' region

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

Disease context

partial androgen insensitivity syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypospadias 1, X-linked Kennedy disease androgen insensitivity syndrome

For Partial androgen insensitivity syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: All ages

Similar variants

AR p.Pro392Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
AR p.Pro392Leu Uncertain significance ★ ⚠ same residue
AR c.1768+2T>C Pathogenic/Likely pathogenic ★★ same condition
AR c.1769-11T>A Pathogenic ★★ same condition
AR c.2450-6C>G Pathogenic ★★ same condition
AR p.Ala588Pro Pathogenic/Likely pathogenic ★★ same condition
AR p.Ala597Thr Pathogenic ★★ same condition
AR p.Ala688Val Pathogenic/Likely 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-pro392ser (accessed [today's date]).

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