Is PRPH2 p.Asn136= (c.408C>T) pathogenic?

PRPH2 p.Asn136= (c.408C>T) is classified Likely benign in PRPH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-03). Very rare (popmax 0.00934%, afr); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Asn136= (c.408C>T)?

PRPH2 p.Asn136= (c.408C>T) is associated with PRPH2-related disorder (ClinVar).

How common is PRPH2 p.Asn136= (c.408C>T) in the general population?

PRPH2 p.Asn136= (c.408C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

PRPH2 p.Asn136=

c.408C>T · rs148513859 · VCV1115154

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

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 -13	GERP -3.6
Overall
CADD	0.185	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,912 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00235% 38/1,614,038 alleles · very rare exomes 32/1,461,892 · genomes 6/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,702
Remaining individualsnot grpmax-eligible	0.008%	12,496
European (non-Finnish)	0.00203%	49,168
Admixed American	0.00167%	59,998
Finnishnot grpmax-eligible	0.00156%	64,034

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.Asn136=
Coding: c.408C>T
MANE Select: NM_000322
dbSNP: rs148513859
Type: single nucleotide variant
Location: chr6:42721927 (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

PRPH2-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPH2 p.Asn136fs Pathogenic/Likely pathogenic ★★ same residue
PRPH2 c.582-1G>A Pathogenic/Likely 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
PRPH2 p.Arg142Trp Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Arg195Leu 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-asn136 (accessed [today's date]).

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