Is CCDC141 p.Ser55Cys (c.163A>T) pathogenic?

CCDC141 p.Ser55Cys (c.163A>T) is classified Uncertain significance in CCDC141 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-28). Ultra-rare (popmax 0.0175%, nfe).

How common is CCDC141 p.Ser55Cys (c.163A>T) in the general population?

CCDC141 p.Ser55Cys (c.163A>T) is ultra-rare (popmax 0.0175%, nfe) (gnomAD).

CCDC141 p.Ser55Cys

c.163A>T · rs755133675 · VCV2575389

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.048	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.36, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 216 kb · p 0.0073 · regional, not allelic
Overall
CADD	19.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0175% European (non-Finnish) · 200/1,144,658 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0198% 306/1,542,546 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.153%	652
Remaining individualsnot grpmax-eligible	0.0235%	4,264
European (non-Finnish)grpmax	0.0175%	5,723
African / African-American	0.00275%	36,396

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.Ser55Cys
Coding: c.163A>T
MANE Select: NM_173648
dbSNP: rs755133675
Type: single nucleotide variant
Location: chr2:179047346 (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.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-ser55cys (accessed [today's date]).

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