Is CSK p.Ala428Thr (c.1282G>A) pathogenic?

CSK p.Ala428Thr (c.1282G>A) is classified Benign in CSK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: likely benign (0.067); Low-frequency (popmax 1.13%, sas).

How common is CSK p.Ala428Thr (c.1282G>A) in the general population?

CSK p.Ala428Thr (c.1282G>A) is low-frequency (popmax 1.13%, sas) (gnomAD).

What do computational predictors say about CSK p.Ala428Thr (c.1282G>A)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

CSK p.Ala428Thr

c.1282G>A · rs147023686 · VCV3024825

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -5.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.028	GERP -0.13
Regional constraint	o/e 0.66	unconstrained · MANE · 462 bp · p 0.00084 · regional, not allelic
Overall
CADD	13.19	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 1.13% South Asian · 1,029/91,012 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.0777% 1,253/1,612,656 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.13%	88
Middle Eastern	0.198%	505
Remaining individualsnot grpmax-eligible	0.0752%	1,329
Admixed American	0.0167%	5,971
European (non-Finnish)	0.0125%	7,971
Finnishnot grpmax-eligible	0.00474%	21,114
African / African-American	0.004%	25,002
East Asian	0.00223%	44,828

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: CSK
Protein: p.Ala428Thr
Coding: c.1282G>A
MANE Select: NM_004383
dbSNP: rs147023686
Type: single nucleotide variant
Location: chr15:74802442 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.57 · 6 PDB
Residue 428: the protein kinase domain; an α-helix

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

Similar variants

CSK p.Gly287Asp Benign ★★ same type
CSK p.Ala407Thr Uncertain significance ★ ⚠ same type
CSK p.Arg56Cys Uncertain significance ★ ⚠ same type
CSK p.Arg56His Uncertain significance ★ ⚠ same type
CSK p.Arg94Gln Uncertain significance ★ ⚠ same type
CSK p.Asn46Lys Uncertain significance ★ ⚠ same type
CSK p.Asn63Ser Uncertain significance ★ ⚠ same type
CSK p.Asp123Asn 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/csk-p-ala428thr (accessed [today's date]).

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