Is AR p.Pro381Ser (c.1141C>T) pathogenic?

AR p.Pro381Ser (c.1141C>T) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.0634); Very rare (popmax 0.00299%, eas); Associated with male infertility.

What condition is associated with AR p.Pro381Ser (c.1141C>T)?

AR p.Pro381Ser (c.1141C>T) is associated with male infertility (ClinVar).

How common is AR p.Pro381Ser (c.1141C>T) in the general population?

AR p.Pro381Ser (c.1141C>T) is very rare (popmax 0.00299%, eas) (gnomAD).

What do computational predictors say about AR p.Pro381Ser (c.1141C>T)?

AlphaMissense predicts likely benign (score 0.0634) — an in-silico prediction, not a clinical call.

AR p.Pro381Ser

c.1141C>T · rs773716161 · VCV3061770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00299%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

male infertility

Computational evidence

Protein change
AlphaMissense	0.0634	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -9.72	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 1.5	GERP 1.7, phastCons 0.23
Overall
CADD	9.621	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00299% East Asian · 1/33,396 alleles

Filtering AF 0.00126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00158% 19/1,203,061 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00299%	33,396
European (non-Finnish)	0.00202%	49,550

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.Pro381Ser
Coding: c.1141C>T
MANE Select: NM_000044
dbSNP: rs773716161
Type: single nucleotide variant
Location: chrX:67546287 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 381: the 'interaction with znf318' region; the 'modulating' region

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

Disease context

male infertility — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AR p.Arg856His Pathogenic/Likely pathogenic ★★ same condition
AR p.Asn757Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
AR p.Tyr408Cys Uncertain significance ★★ ⚠ same condition
AR p.Arg618Trp Likely pathogenic ★ same condition
AR p.Arg787Gln Likely pathogenic ★ same condition
AR p.Asp829Val Pathogenic ★ same condition
AR p.Cys687Arg Pathogenic ★ ⚠ same condition
AR p.Ala159Thr Conflicting classifications of pathogenicity ★ 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-pro381ser (accessed [today's date]).

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