Is CCDC144A p.Pro252Gln (c.755C>A) pathogenic?

CCDC144A p.Pro252Gln (c.755C>A) is classified Uncertain significance in CCDC144A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.1071); Rare (popmax 0.392%, eas).

How common is CCDC144A p.Pro252Gln (c.755C>A) in the general population?

CCDC144A p.Pro252Gln (c.755C>A) is rare (popmax 0.392%, eas) (gnomAD).

What do computational predictors say about CCDC144A p.Pro252Gln (c.755C>A)?

AlphaMissense predicts likely benign (score 0.1071) — an in-silico prediction, not a clinical call.

CCDC144A p.Pro252Gln

c.755C>A · rs765491212 · VCV2222659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1071 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.392%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1071	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -5.60	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 -2
Regional constraint	o/e 0.69	unconstrained · MANE · 6,456 bp · p 1.2e-09 · regional, not allelic
Overall
CADD	7.224	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

Grpmax group 0.392% East Asian · 176/44,850 alleles

Filtering AF 0.345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.327%

Overall 0.0109% 176/1,611,684 alleles · 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: CCDC144A
Protein: p.Pro252Gln
Coding: c.755C>A
MANE Select: NM_001382000
dbSNP: rs765491212
Type: single nucleotide variant
Location: chr17:16708812 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 61.65
Residue 252: the 'disordered' region

Full CCDC144A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC144A p.Ala1033Ser Uncertain significance ★ ⚠ same type
CCDC144A p.Ala1080Val Uncertain significance ★ ⚠ same type
CCDC144A p.Ala1121Ser Uncertain significance ★ ⚠ same type
CCDC144A p.Ala1195Thr Uncertain significance ★ ⚠ same type
CCDC144A p.Ala1206Ser Uncertain significance ★ ⚠ same type
CCDC144A p.Ala1206Val Uncertain significance ★ ⚠ same type
CCDC144A p.Ala1381Gly Uncertain significance ★ ⚠ same type
CCDC144A p.Ala1382= 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/ccdc144a-p-pro252gln (accessed [today's date]).

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