Is AR p.Ser343Phe (c.1028C>T) pathogenic?

AR p.Ser343Phe (c.1028C>T) is classified Uncertain significance in AR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-16). AlphaMissense: likely benign (0.21); Very rare (popmax 0.00217%, amr); Associated with Inborn genetic diseases.

What condition is associated with AR p.Ser343Phe (c.1028C>T)?

AR p.Ser343Phe (c.1028C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AR p.Ser343Phe (c.1028C>T) in the general population?

AR p.Ser343Phe (c.1028C>T) is very rare (popmax 0.00217%, amr) (gnomAD).

What do computational predictors say about AR p.Ser343Phe (c.1028C>T)?

AlphaMissense predicts likely benign (score 0.21) — an in-silico prediction, not a clinical call.

AR p.Ser343Phe

c.1028C>T · VCV3935758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.21 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.21	likely benign
REVEL	0.59	indeterminate
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.1, phastCons 0.99
Overall
CADD	22.2	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 0.00217% Admixed American · 1/46,175 alleles

Overall 9.11e-05% 1/1,097,906 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.Ser343Phe
Coding: c.1028C>T
MANE Select: NM_000044
Type: single nucleotide variant
Location: chrX:67546174 (GRCh38)
Structure: AlphaFold pLDDT 58.85 · 95 PDB
Residue 343: the 'interaction with znf318' region; the 'modulating' 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.Ser343= Benign ★★ same residue
AR p.Leu446Trp Uncertain significance ★★ ⚠ same condition
AR p.Gly471= Likely benign ★★ same condition
AR p.Ser343fs Pathogenic ★ same residue
AR p.Ala151Glu Uncertain significance ★ ⚠ same condition
AR p.Ala253Gly Uncertain significance ★ ⚠ same condition
AR p.Ala331Asp Uncertain significance ★ ⚠ same condition
AR p.Ala358Glu 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-ser343phe (accessed [today's date]).

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