Is PRPH2 p.Ala339fs (c.1014_1015insCTGCGCCCTCGGCTTCCAC) pathogenic?

PRPH2 p.Ala339fs (c.10141015insCTGCGCCCTCGGCTTCCAC) is classified Uncertain significance in PRPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-07).

PRPH2 p.Ala339fs

c.1014_1015insCTGCGCCCTCGGCTTCCAC · VCV4891941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.58, phastCons 0.82

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: PRPH2
Protein: p.Ala339fs
Coding: c.1014_1015insCTGCGCCCTCGGCTTCCAC
MANE Select: NM_000322
Type: Insertion
Location: chr6:42698321 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB

Full PRPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPH2 p.Ala339_Gly340dup Uncertain significance ★ same residue
PRPH2 p.Ala339Gly Uncertain significance ★ same residue
PRPH2 p.Ala339Thr Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Ser259_Ser260insLeu Uncertain significance ★★ same type
PRPH2 p.Gln304fs Likely pathogenic ★ same type
PRPH2 p.Phe74fs Pathogenic ★ same type
PRPH2 p.Val14fs Pathogenic ★ same type
PRPH2 p.Val200_Asp201insGlyProSerProValSerLeuSerLeuSerArgLeuProLeuProLeuProSerProSerProAlaProGluThrHisThrArgSerLeuIleGlnLeuProXaaXaaXaaXaaLysLysLysLysLysLysLysSerAsnVal Pathogenic ★ 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/prph2-p-ala339fs (accessed [today's date]).

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