Is PRLR p.Pro495Ser (c.1483C>T) pathogenic?

PRLR p.Pro495Ser (c.1483C>T) is classified Uncertain significance in PRLR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-22). AlphaMissense: likely benign (0.084); Absent from gnomAD v4.1; Associated with familial hyperprolactinemia.

What condition is associated with PRLR p.Pro495Ser (c.1483C>T)?

PRLR p.Pro495Ser (c.1483C>T) is associated with familial hyperprolactinemia (ClinVar).

How common is PRLR p.Pro495Ser (c.1483C>T) in the general population?

PRLR p.Pro495Ser (c.1483C>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial hyperprolactinemia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PRLR p.Pro495Ser (c.1483C>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

PRLR p.Pro495Ser

c.1483C>T · rs772553198 · VCV1526078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial hyperprolactinemia

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -5.90	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 2.1	GERP -0.28, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 5,076 bp · p 0.31 · regional, not allelic
Overall
CADD	14.16	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

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: PRLR
Protein: p.Pro495Ser
Coding: c.1483C>T
MANE Select: NM_000949
dbSNP: rs772553198
Type: single nucleotide variant
Location: chr5:35065475 (GRCh38)
Gene constraint: LOEUF 0.438 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.67 · 12 PDB
Residue 495: the 'disordered' region

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

Disease context

familial hyperprolactinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial hyperprolactinemia (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

PRLR p.Ile79Val Uncertain significance ★★ ⚠ same condition
PRLR p.Thr490Met Uncertain significance ★★ ⚠ same condition
PRLR p.Ala281Val Uncertain significance ★ ⚠ same condition
PRLR p.Asn40Ser Uncertain significance ★ ⚠ same condition
PRLR p.Arg171Ter Pathogenic same condition
PRLR p.His212Arg Pathogenic ⚠ same condition
PRLR p.Pro269Leu Pathogenic same condition
PRLR p.Glu485Ala Uncertain significance ★★ ⚠ 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/prlr-p-pro495ser (accessed [today's date]).

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