Is CCDC141 p.Val1516= (c.4548C>T) pathogenic?

CCDC141 p.Val1516= (c.4548C>T) is classified Benign in CCDC141 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-29). Common (popmax 22.3%, afr) — too common for a highly-penetrant pathogenic allele.

CCDC141 p.Val1516=

Q: How common is CCDC141 p.Val1516= (c.4548C>T) in the general population?

CCDC141 p.Val1516= (c.4548C>T) is common (popmax 22.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4548C>T · rs16866554 · VCV1272099

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 22.3%, afr) — too common for a highly-penetrant pathogenic allele

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 4.5	GERP 1.4, phastCons 1
Overall
CADD	8.837	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.3% African / African-American · 16,288/73,074 alleles

Filtering AF 22% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.9%

Overall 7.58% 116,402/1,536,036 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.3%	4
East Asian	14%	7
Ashkenazi Jewishnot grpmax-eligible	12.9%	8
Middle Eastern	11.3%	9
Remaining individualsnot grpmax-eligible	8.65%	12
South Asian	7.89%	13
Amishnot grpmax-eligible	7.24%	14
Finnishnot grpmax-eligible	7.04%	14
European (non-Finnish)	6.26%	16
Admixed American	6.17%	16

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.Val1516=
Coding: c.4548C>T
MANE Select: NM_173648
dbSNP: rs16866554
Type: single nucleotide variant
Location: chr2:178834218 (GRCh38)
Gene constraint: LOEUF 1.052 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36
Residue 1516: the ig-like domain

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

Similar variants

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
CCDC141 p.Arg468Gln 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-val1516 (accessed [today's date]).

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