Is CKLF p.Asp124Glu (c.372C>G) pathogenic?

CKLF p.Asp124Glu (c.372C>G) is classified Uncertain significance in CKLF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely pathogenic (0.9263); Very rare (popmax 0.00223%, eas).

How common is CKLF p.Asp124Glu (c.372C>G) in the general population?

CKLF p.Asp124Glu (c.372C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CKLF p.Asp124Glu (c.372C>G)?

AlphaMissense predicts likely pathogenic (score 0.9263) — an in-silico prediction, not a clinical call.

CKLF p.Asp124Glu

c.372C>G · rs755740119 · VCV3145250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9263	likely pathogenic
REVEL	0.342	indeterminate
SaProt	LLR -7.88	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 -8.8	GERP -3.3
Regional constraint	o/e 0.91	unconstrained · MANE · 13 kb · p 0.23 · regional, not allelic
Overall
CADD	8.224	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

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Overall 6.84e-05% 1/1,461,798 alleles · very rare

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: CKLF
Protein: p.Asp124Glu
Coding: c.372C>G
MANE Select: NM_016951
dbSNP: rs755740119
Type: single nucleotide variant
Location: chr16:66565924 (GRCh38)
Gene constraint: LOEUF 1.716 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.68
Residue 124: the marvel domain

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

Similar variants

CKLF p.Asp124Gly Uncertain significance ★ ⚠ same residue
CKLF p.Val145= Benign ★★ same type
CKLF-CMTM1 p.His10Tyr Uncertain significance ★ ⚠ same type
CKLF-CMTM1 p.Ile56Val Uncertain significance ★ ⚠ same type
CKLF-CMTM1 p.Phe13Leu Uncertain significance ★ ⚠ same type
CKLF p.Ala126Val Uncertain significance ★ ⚠ same type
CKLF p.Arg130Gly Uncertain significance ★ ⚠ same type
CKLF p.Gly125Arg Uncertain significance ★ ⚠ 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/cklf-p-asp124glu (accessed [today's date]).

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