Is CRISPLD2 p.Pro124= (c.372G>C) pathogenic?

CRISPLD2 p.Pro124= (c.372G>C) is classified Likely benign in CRISPLD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-09). Rare (popmax 0.243%, afr); Associated with CRISPLD2-related disorder.

What condition is associated with CRISPLD2 p.Pro124= (c.372G>C)?

CRISPLD2 p.Pro124= (c.372G>C) is associated with CRISPLD2-related disorder (ClinVar).

How common is CRISPLD2 p.Pro124= (c.372G>C) in the general population?

CRISPLD2 p.Pro124= (c.372G>C) is rare (popmax 0.243%, afr) (gnomAD).

CRISPLD2 p.Pro124=

c.372G>C · rs140214661 · VCV3044536

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.243%, afr)

Conditions

CRISPLD2-related disorder

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 -20	GERP -4.6
Overall
CADD	0.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.243% African / African-American · 182/75,036 alleles

Filtering AF 0.214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.203%

Overall 0.0117% 188/1,613,580 alleles · rare exomes 71/1,461,258 · genomes 117/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.243%	412
Remaining individualsnot grpmax-eligible	0.0032%	31,230
South Asian	0.0022%	45,524
Admixed American	0.00167%	60,012
European (non-Finnish)	8.48e-05%	1,179,617

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: CRISPLD2
Protein: p.Pro124=
Coding: c.372G>C
MANE Select: NM_031476
dbSNP: rs140214661
Type: single nucleotide variant
Location: chr16:84849397 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.67
Residue 124: the scp domain

Full CRISPLD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CRISPLD2-related disorder

Similar variants

CRISPLD2 p.Pro124Ala Uncertain significance ★ same residue
CRISPLD2 p.Gln69His Uncertain significance ⚠ same condition
CRISPLD2 c.1157-9T>C Benign same condition
CRISPLD2 c.1305+7A>C Likely benign same condition
CRISPLD2 c.360-7C>T Likely benign same condition
CRISPLD2 c.709+7A>G Benign same condition
CRISPLD2 c.915-5G>A Likely benign same condition
CRISPLD2 p.Ala446= Likely benign same condition

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/crispld2-p-pro124 (accessed [today's date]).

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