Is CERKL p.Pro2Thr (c.4C>A) pathogenic?

CERKL p.Pro2Thr (c.4C>A) is classified Uncertain significance in CERKL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). AlphaMissense: likely benign (0.1214); No allele count reported in gnomAD v4.1 (AN 1,580,112).

How common is CERKL p.Pro2Thr (c.4C>A) in the general population?

CERKL p.Pro2Thr (c.4C>A) is no allele count reported in gnomAD v4.1 (AN 1,580,112) (gnomAD).

What do computational predictors say about CERKL p.Pro2Thr (c.4C>A)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

CERKL p.Pro2Thr

c.4C>A · rs1465218546 · VCV2087554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,580,112)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.26	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 3.2	GERP -2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 119 kb · p 0.45 · regional, not allelic
Overall
CADD	18.97	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,580,112). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CERKL
Protein: p.Pro2Thr
Coding: c.4C>A
MANE Select: NM_201548
dbSNP: rs1465218546
Type: single nucleotide variant
Location: chr2:181657003 (GRCh38)
Gene constraint: LOEUF 1.43 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82
Residue 2: the 'disordered' region

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

Similar variants

CERKL p.Pro2= Likely benign ★ same residue
CERKL c.1074-1G>C Pathogenic/Likely pathogenic ★★ same type
CERKL c.1074-2A>C Likely pathogenic ★★ same type
CERKL c.1074-2A>G Likely pathogenic ★★ same type
CERKL c.1365+1G>A Likely pathogenic ★★ same type
CERKL c.1366-1G>A Likely pathogenic ★★ same type
CERKL c.1366-1G>T Likely pathogenic ★★ same type
CERKL c.1366-2A>G Likely 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/cerkl-p-pro2thr (accessed [today's date]).

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