Is PRPH p.Gln307Ter (c.919C>T) pathogenic?

PRPH p.Gln307Ter (c.919C>T) is classified Likely pathogenic in PRPH (ClinVar, Single submitter, 1 submitter). Very rare (popmax 8.47e-05%, nfe); Associated with amyotrophic lateral sclerosis type 1.

What condition is associated with PRPH p.Gln307Ter (c.919C>T)?

PRPH p.Gln307Ter (c.919C>T) is associated with amyotrophic lateral sclerosis type 1 (ClinVar).

How common is PRPH p.Gln307Ter (c.919C>T) in the general population?

PRPH p.Gln307Ter (c.919C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

PRPH p.Gln307Ter

c.919C>T · rs2498984328 · VCV3234975

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

amyotrophic lateral sclerosis type 1

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 5 of 9
REVEL	0.089	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.74, phastCons 1
Overall
CADD	43.0	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,002 alleles

Overall 6.2e-05% 1/1,614,050 alleles · very rare exomes 1/1,461,814 · genomes 0/152,236 · joint denominator

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: PRPH
Protein: p.Gln307Ter
Coding: c.919C>T
MANE Select: NM_006262
dbSNP: rs2498984328
Type: single nucleotide variant
Location: chr12:49297196 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.24
Residue 307: the if rod domain; the 'coil 2' region

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

Disease context

amyotrophic lateral sclerosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPH p.Arg9Gln Benign ★★ same condition
PRPH p.Gln249Ter Likely pathogenic ★ same condition
PRPH c.607-1G>A Conflicting classifications of pathogenicity ★ same condition
PRPH p.His232Arg Uncertain significance ★ ⚠ same condition
PRPH p.Thr422Ala Uncertain significance ★ ⚠ same condition
PRPH p.Glu233Lys Uncertain significance ★★ ⚠ same type
PRPH p.Ile419Met Uncertain significance ★★ ⚠ same type
PRPH c.1267+58T>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-gln307ter (accessed [today's date]).

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