Is CCDC14 p.Lys34Arg (c.101A>G) pathogenic?

CCDC14 p.Lys34Arg (c.101A>G) is classified Uncertain significance in CCDC14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). Ultra-rare (popmax 0.0109%, nfe).

How common is CCDC14 p.Lys34Arg (c.101A>G) in the general population?

CCDC14 p.Lys34Arg (c.101A>G) is ultra-rare (popmax 0.0109%, nfe) (gnomAD).

CCDC14 p.Lys34Arg

c.101A>G · rs781513961 · VCV2566166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.145	moderately benign-leaning
Splicing
SpliceAI	Δ0.26	acceptor gain, 14 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3.2	GERP 0.51, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 46 kb · p 0.97 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% European (non-Finnish) · 125/1,144,040 alleles

Filtering AF 0.00934% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00871%

Overall 0.00873% 135/1,545,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0134%	7,480
European (non-Finnish)grpmax	0.0109%	9,152
African / African-American	0.00274%	36,432

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: CCDC14
Protein: p.Lys34Arg
Coding: c.101A>G
MANE Select: NM_001366335
dbSNP: rs781513961
Type: single nucleotide variant
Location: chr3:123956413 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.45

Full CCDC14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC14 c.38G>A Uncertain significance ★ same type
CCDC14 c.-20C>T Uncertain significance ★ same type
CCDC14 c.-30T>C Uncertain significance ★ same type
CCDC14 c.-32C>T Uncertain significance ★ same type
CCDC14 c.-33C>T Uncertain significance ★ same type
CCDC14 c.-5G>A Uncertain significance ★ same type
CCDC14 p.Ala636Pro Uncertain significance ★ same type
CCDC14 p.Ala636Val 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/ccdc14-p-lys34arg (accessed [today's date]).

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