Is CLRN1 p.Trp33Ter (c.98G>A) pathogenic?

CLRN1 p.Trp33Ter (c.98G>A) is classified Likely pathogenic in CLRN1 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.000593%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with CLRN1 p.Trp33Ter (c.98G>A)?

CLRN1 p.Trp33Ter (c.98G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is CLRN1 p.Trp33Ter (c.98G>A) in the general population?

CLRN1 p.Trp33Ter (c.98G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

CLRN1 p.Trp33Ter

c.98G>A · rs878853379 · VCV236488

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

inherited retinal dystrophy

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 3
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Overall
CADD	40.0	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 0.000593% European (non-Finnish) · 7/1,180,046 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000616% 9/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)grpmax	0.000593%	168,578

Remaining individuals 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: CLRN1
Protein: p.Trp33Ter
Coding: c.98G>A
MANE Select: NM_174878
dbSNP: rs878853379
Type: single nucleotide variant
Location: chr3:150972611 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.74

Full CLRN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLRN1 p.Asn202Lys Pathogenic/Likely pathogenic ★★ same condition
CLRN1 c.433+1083A>G Uncertain significance ★★ same condition
CLRN1 p.Gln73Arg Uncertain significance ★★ ⚠ same condition
CLRN1 p.Gly136Glu Uncertain significance ★★ ⚠ same condition
CLRN1 p.Pro134Leu Uncertain significance ★★ ⚠ same condition
CLRN1 p.Thr223Ile Uncertain significance ★★ ⚠ same condition
CLRN1 p.Thr224Ala Uncertain significance ★★ ⚠ same condition
CLRN1 p.Ala19= Benign/Likely benign ★★ 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/clrn1-p-trp33ter (accessed [today's date]).

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