Is PRPH2 p.Val106= (c.318T>C) pathogenic?

PRPH2 p.Val106= (c.318T>C) is classified Benign in PRPH2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 65.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Val106= (c.318T>C)?

PRPH2 p.Val106= (c.318T>C) is associated with PRPH2-related disorder, fundus albipunctatus, patterned macular dystrophy 1 (ClinVar).

PRPH2 p.Val106=

Q: How common is PRPH2 p.Val106= (c.318T>C) in the general population?

PRPH2 p.Val106= (c.318T>C) is common (popmax 65.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.318T>C · rs7764439 · VCV92846

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 65.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.12	GERP -3.1, phastCons 0.36
Overall
CADD	2.461	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 65.7% African / African-American · 49,234/74,906 alleles

Filtering AF 65.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 65%

Overall 57.6% 930,013/1,613,784 alleles · common exomes 839,587/1,461,860 · genomes 90,426/151,924 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	73.4%	1
African / African-Americangrpmax	65.7%	2
Middle Eastern	62.8%	2
Admixed American	60%	2
Remaining individualsnot grpmax-eligible	57.8%	2
European (non-Finnish)	57.6%	2
Finnishnot grpmax-eligible	56.1%	2
South Asian	53.6%	2
East Asian	53.4%	2
Ashkenazi Jewishnot grpmax-eligible	52.3%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PRPH2
Protein: p.Val106=
Coding: c.318T>C
MANE Select: NM_000322
dbSNP: rs7764439
Type: single nucleotide variant
Location: chr6:42722017 (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

Disease context

Also linked: fundus albipunctatus patterned macular dystrophy 1 retinitis pigmentosa 7 adult-onset foveomacular vitelliform dystrophy choroidal dystrophy, central areolar 2 cone-rod dystrophy inherited retinal dystrophy retinitis pigmentosa vitelliform macular dystrophy 3

Similar variants

PRPH2 p.Val106fs Pathogenic same residue
PRPH2 c.581+1G>A Pathogenic ★★ same condition
PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.582-2A>T Pathogenic ★★ same condition
PRPH2 c.828+1G>A Pathogenic ★★ same condition
PRPH2 c.828+1G>T Pathogenic ★★ same condition
PRPH2 c.828+2T>C Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.828+3A>T Pathogenic ★★ 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/prph2-p-val106 (accessed [today's date]).

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