Is PRLR p.Ile79Val (c.235A>G) pathogenic?

PRLR p.Ile79Val (c.235A>G) is classified Uncertain significance in PRLR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-20). AlphaMissense: likely benign (0.0671); Very rare (popmax 0.00373%, nfe); Associated with familial hyperprolactinemia.

What condition is associated with PRLR p.Ile79Val (c.235A>G)?

PRLR p.Ile79Val (c.235A>G) is associated with familial hyperprolactinemia, multiple fibroadenoma of the breast (ClinVar).

How common is PRLR p.Ile79Val (c.235A>G) in the general population?

PRLR p.Ile79Val (c.235A>G) is very rare (popmax 0.00373%, nfe) (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.Ile79Val (c.235A>G)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

PRLR p.Ile79Val

c.235A>G · VCV3310228

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial hyperprolactinemia

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -5.02	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 -1.6	GERP -3.1
Regional constraint	o/e 0.76	unconstrained · MANE · 19 kb · p 0.00022 · regional, not allelic
Overall
CADD	2.295	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 0.00373% European (non-Finnish) · 44/1,178,886 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00292% 47/1,611,074 alleles · very rare exomes 40/1,458,858 · genomes 7/152,216 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,793
South Asian	0.00222%	45,143
Admixed American	0.00168%	59,490

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: PRLR
Protein: p.Ile79Val
Coding: c.235A>G
MANE Select: NM_000949
Type: single nucleotide variant
Location: chr5:35084608 (GRCh38)
Gene constraint: LOEUF 0.438 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.67 · 12 PDB
Residue 79: the fibronectin type-iii 1 domain

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

Also linked: multiple fibroadenoma of the breast

For Familial hyperprolactinemia (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

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PRLR p.Asn40Ser Uncertain significance ★ ⚠ same condition
PRLR p.Pro495Ser Uncertain significance ★ ⚠ same condition
PRLR p.Arg171Ter Pathogenic same condition
PRLR p.His212Arg Pathogenic ⚠ same condition
PRLR p.Pro269Leu Pathogenic same condition
PRLR p.Ile170Leu 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/prlr-p-ile79val (accessed [today's date]).

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