Is CRKL p.Ser42= (c.126C>T) pathogenic?

CRKL p.Ser42= (c.126C>T) is classified Likely benign in CRKL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-20). Very rare (popmax 0.0022%, sas).

How common is CRKL p.Ser42= (c.126C>T) in the general population?

CRKL p.Ser42= (c.126C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

CRKL p.Ser42=

c.126C>T · rs1929756463 · VCV1996769

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 2.1, phastCons 1
Overall
CADD	15.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,092 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000124% 2/1,614,154 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: CRKL
Protein: p.Ser42=
Coding: c.126C>T
MANE Select: NM_005207
dbSNP: rs1929756463
Type: single nucleotide variant
Location: chr22:20918060 (GRCh38)
Gene constraint: LOEUF 0.316 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 69.65 · 6 PDB
Residue 42: the sh2 domain; a β-strand

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

Similar variants

CRKL p.Ala226Val Uncertain significance ★★ ⚠ same type
CRKL p.Arg169Gln Uncertain significance ★★ ⚠ same type
CRKL p.Asn137Ser Uncertain significance ★★ ⚠ same type
CRKL p.Ile263Thr Uncertain significance ★★ ⚠ same type
CRKL p.Val178Ile Uncertain significance ★★ ⚠ same type
CRKL c.311+12C>T Likely benign ★★ same type
CRKL p.Gly221Ser Benign ★★ same type
CRKL p.Ser12= 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/crkl-p-ser42 (accessed [today's date]).

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