Is CCDC14 p.Arg37His (c.110G>A) pathogenic?

CCDC14 p.Arg37His (c.110G>A) is classified Likely benign in CCDC14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). Very rare (popmax 0.00991%, amr).

How common is CCDC14 p.Arg37His (c.110G>A) in the general population?

CCDC14 p.Arg37His (c.110G>A) is very rare (popmax 0.00991%, amr) (gnomAD).

CCDC14 p.Arg37His

c.110G>A · VCV3996460

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00991%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.016	strongly benign-leaning
Splicing
SpliceAI	Δ0.29	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -2.5	GERP -1.1
Regional constraint	o/e 1.00	unconstrained · MANE · 46 kb · p 0.97 · regional, not allelic
Overall
CADD	0.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00991% Admixed American · 5/50,450 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00259%

Overall 0.0042% 65/1,546,866 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.015%	6,658
Admixed Americangrpmax	0.00991%	10,090
African / African-American	0.00686%	14,576
European (non-Finnish)	0.00384%	26,018
East Asian	0.00246%	40,732
South Asian	0.00121%	82,846

Remaining individuals 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.Arg37His
Coding: c.110G>A
MANE Select: NM_001366335
Type: single nucleotide variant
Location: chr3:123956404 (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-arg37his (accessed [today's date]).

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