Is CCDC141 p.Pro1064= (c.3192G>A) pathogenic?

CCDC141 p.Pro1064= (c.3192G>A) is classified Likely benign in CCDC141 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Very rare (popmax 0.005%, amr).

How common is CCDC141 p.Pro1064= (c.3192G>A) in the general population?

CCDC141 p.Pro1064= (c.3192G>A) is very rare (popmax 0.005%, amr) (gnomAD).

CCDC141 p.Pro1064=

c.3192G>A · rs151235903 · VCV2887915

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 0.27	GERP -5.1, phastCons 0.39
Overall
CADD	1.444	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,998 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.012% 194/1,613,962 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.184%	543
Remaining individualsnot grpmax-eligible	0.024%	4,166
Admixed Americangrpmax	0.005%	19,999
European (non-Finnish)	0.00466%	21,454
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,876
South Asian	0.0011%	91,076

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCDC141
Protein: p.Pro1064=
Coding: c.3192G>A
MANE Select: NM_173648
dbSNP: rs151235903
Type: single nucleotide variant
Location: chr2:178853493 (GRCh38)
Gene constraint: LOEUF 1.052 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36

Full CCDC141 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC141 p.Pro1064Leu Conflicting classifications of pathogenicity ★ same residue
CCDC141 p.Ala1261Val Uncertain significance ★★ same type
CCDC141 p.Ala88Thr Uncertain significance ★★ same type
CCDC141 p.Arg1346Trp Uncertain significance ★★ same type
CCDC141 p.Arg1463Ser Uncertain significance ★★ same type
CCDC141 p.Arg1482Trp Uncertain significance ★★ same type
CCDC141 p.Arg180Trp Uncertain significance ★★ same type
CCDC141 p.Arg287Gln 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/ccdc141-p-pro1064 (accessed [today's date]).

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