Is CLCNKB p.Pro341Ser (c.1021C>T) pathogenic?

CLCNKB p.Pro341Ser (c.1021C>T) is classified Uncertain significance in CLCNKB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely pathogenic (0.6194); Absent from gnomAD v4.1.

How common is CLCNKB p.Pro341Ser (c.1021C>T) in the general population?

CLCNKB p.Pro341Ser (c.1021C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLCNKB p.Pro341Ser (c.1021C>T)?

AlphaMissense predicts likely pathogenic (score 0.6194) — an in-silico prediction, not a clinical call.

CLCNKB p.Pro341Ser

c.1021C>T · rs2124098826 · VCV1346430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6194 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6194	likely pathogenic
REVEL	0.601	indeterminate
SaProt	LLR -9.76	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.0014 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: CLCNKB
Protein: p.Pro341Ser
Coding: c.1021C>T
MANE Select: NM_000085
dbSNP: rs2124098826
Type: single nucleotide variant
Location: chr1:16050568 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.16

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

Similar variants

CLCNKB c.968+1G>A Pathogenic/Likely pathogenic ★★ same type
CLCNKB p.Ala204Thr Pathogenic/Likely pathogenic ★★ same type
CLCNKB p.Ala77Pro Pathogenic/Likely pathogenic ★★ same type
CLCNKB p.Arg304Ter Pathogenic/Likely pathogenic ★★ same type
CLCNKB p.Arg438His Pathogenic ★★ same type
CLCNKB p.Arg595Ter Pathogenic ★★ same type
CLCNKB p.Arg76Ter Pathogenic ★★ same type
CLCNKB p.Glu225Ter Pathogenic ★★ 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/clcnkb-p-pro341ser (accessed [today's date]).

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