Is CCDC14 p.Ser785Phe (c.2354C>T) pathogenic?

CCDC14 p.Ser785Phe (c.2354C>T) is classified Uncertain significance in CCDC14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). Rare (popmax 0.346%, mid).

How common is CCDC14 p.Ser785Phe (c.2354C>T) in the general population?

CCDC14 p.Ser785Phe (c.2354C>T) is rare (popmax 0.346%, mid) (gnomAD).

CCDC14 p.Ser785Phe

c.2354C>T · rs147561384 · VCV2352234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.346%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.045	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -1.5, phastCons 0.98
Regional constraint	o/e 1.00	unconstrained · MANE · 46 kb · p 0.97 · regional, not allelic
Overall
CADD	19.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.346% Middle Eastern · 21/6,062 alleles

Filtering AF 0.232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.0485% 782/1,613,890 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.415%	241
Middle Easterngrpmax	0.346%	289
Admixed American	0.128%	779
Remaining individualsnot grpmax-eligible	0.088%	1,136
European (non-Finnish)	0.0411%	2,433
South Asian	0.0154%	6,505
East Asian	0.00446%	22,444
African / African-American	0.004%	25,018
Finnishnot grpmax-eligible	0.00312%	32,003

Ashkenazi Jewish 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.Ser785Phe
Coding: c.2354C>T
MANE Select: NM_001366335
dbSNP: rs147561384
Type: single nucleotide variant
Location: chr3:123915143 (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-ser785phe (accessed [today's date]).

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