Is CCDC178 p.Arg116= (c.348G>A) pathogenic?

CCDC178 p.Arg116= (c.348G>A) is classified Likely benign in CCDC178 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-01-01). Rare (popmax 0.841%, mid).

How common is CCDC178 p.Arg116= (c.348G>A) in the general population?

CCDC178 p.Arg116= (c.348G>A) is rare (popmax 0.841%, mid) (gnomAD).

CCDC178 p.Arg116=

c.348G>A · rs147462915 · VCV2648636

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.841%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.21	GERP -3.5, phastCons 0.019
Overall
CADD	14.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.841% Middle Eastern · 50/5,944 alleles

Filtering AF 0.794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.788%

Overall 0.711% 11,198/1,575,728 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.28%	78
Middle Easterngrpmax	0.841%	119
European (non-Finnish)	0.808%	124
Admixed American	0.726%	138
Remaining individualsnot grpmax-eligible	0.722%	138
South Asian	0.436%	229
African / African-American	0.157%	638
Finnishnot grpmax-eligible	0.121%	825
East Asian	0.00475%	21,055

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: CCDC178
Protein: p.Arg116=
Coding: c.348G>A
MANE Select: NM_001105528
dbSNP: rs147462915
Type: single nucleotide variant
Location: chr18:33370050 (GRCh38)
Gene constraint: LOEUF 1.347 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.69

Full CCDC178 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC178 p.Lys515Arg Uncertain significance ★★ ⚠ same type
CCDC178 p.Ala216Thr Uncertain significance ★ ⚠ same type
CCDC178 p.Ala261Gly Uncertain significance ★ ⚠ same type
CCDC178 p.Ala339Asp Uncertain significance ★ ⚠ same type
CCDC178 p.Ala339Thr Uncertain significance ★ ⚠ same type
CCDC178 p.Ala375Thr Uncertain significance ★ ⚠ same type
CCDC178 p.Ala563Thr Uncertain significance ★ ⚠ same type
CCDC178 p.Ala574Glu 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/ccdc178-p-arg116 (accessed [today's date]).

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