Is CERKL p.Phe348Ser (c.1043T>C) pathogenic?

CERKL p.Phe348Ser (c.1043T>C) is classified Conflicting classifications of pathogenicity in CERKL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-08). AlphaMissense: likely pathogenic (0.7239); Very rare (popmax 6.2e-05%); Associated with CERKL-related disorders.

What condition is associated with CERKL p.Phe348Ser (c.1043T>C)?

CERKL p.Phe348Ser (c.1043T>C) is associated with CERKL-related disorders, retinitis pigmentosa 26 (ClinVar).

How common is CERKL p.Phe348Ser (c.1043T>C) in the general population?

CERKL p.Phe348Ser (c.1043T>C) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about CERKL p.Phe348Ser (c.1043T>C)?

AlphaMissense predicts likely pathogenic (score 0.7239) — an in-silico prediction, not a clinical call.

CERKL p.Phe348Ser

c.1043T>C · rs1687844821 · VCV1026139

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7239 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CERKL-related disorders

Computational evidence

Protein change
AlphaMissense	0.7239	likely pathogenic
REVEL	0.377	indeterminate
SaProt	LLR -12.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 119 kb · p 0.45 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F374S vs ClinVar F348S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,020 alleles · very rare exomes 1/1,461,694 · genomes 0/152,326 · 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: CERKL
Protein: p.Phe348Ser
Coding: c.1043T>C
MANE Select: NM_201548
dbSNP: rs1687844821
Type: single nucleotide variant
Location: chr2:181548710 (GRCh38)
Gene constraint: LOEUF 1.43 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82

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

Disease context

CERKL-related disorders

Also linked: retinitis pigmentosa 26

Similar variants

CERKL c.1074-1G>C Pathogenic/Likely pathogenic ★★ same condition
CERKL c.1074-2A>C Likely pathogenic ★★ same condition
CERKL c.1074-2A>G Likely pathogenic ★★ same condition
CERKL c.1365+1G>A Likely pathogenic ★★ same condition
CERKL c.1366-1G>A Likely pathogenic ★★ same condition
CERKL c.1366-1G>T Likely pathogenic ★★ same condition
CERKL c.1366-2A>G Likely pathogenic ★★ same condition
CERKL c.238+1G>A 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/cerkl-p-phe348ser (accessed [today's date]).

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