Is PRPH p.Arg64Ter (c.190C>T) pathogenic?

PRPH p.Arg64Ter (c.190C>T) is classified Uncertain significance in PRPH (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-31). Absent from gnomAD v4.1; Associated with amyotrophic lateral sclerosis.

What condition is associated with PRPH p.Arg64Ter (c.190C>T)?

PRPH p.Arg64Ter (c.190C>T) is associated with amyotrophic lateral sclerosis (ClinVar).

How common is PRPH p.Arg64Ter (c.190C>T) in the general population?

PRPH p.Arg64Ter (c.190C>T) is absent from gnomAD v4.1 (gnomAD).

How is Amyotrophic lateral sclerosis inherited?

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

PRPH p.Arg64Ter

c.190C>T · rs1943161245 · VCV873306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

amyotrophic lateral sclerosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.8, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: PRPH
Protein: p.Arg64Ter
Coding: c.190C>T
MANE Select: NM_006262
dbSNP: rs1943161245
Type: single nucleotide variant
Location: chr12:49295390 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.24
Residue 64: the 'head' region

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

Disease context

amyotrophic lateral sclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Amyotrophic lateral sclerosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

PRPH p.Asp141Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
PRPH p.Glu233Lys Uncertain significance ★★ ⚠ same type
PRPH p.Ile419Met Uncertain significance ★★ ⚠ same type
PRPH c.1267+58T>C Benign ★★ same type
PRPH c.1268-34T>C Benign ★★ same type
PRPH c.703-163T>C Benign ★★ same type
PRPH c.996+1G>A Benign/Likely benign ★★ same type
PRPH c.-24G>C Benign ★★ 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/prph-p-arg64ter (accessed [today's date]).

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