Is CCDC178 p.Arg504His (c.1511G>A) pathogenic?

CCDC178 p.Arg504His (c.1511G>A) is classified Uncertain significance in CCDC178 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely benign (0.0788); Ultra-rare (popmax 0.0362%, afr).

How common is CCDC178 p.Arg504His (c.1511G>A) in the general population?

CCDC178 p.Arg504His (c.1511G>A) is ultra-rare (popmax 0.0362%, afr) (gnomAD).

What do computational predictors say about CCDC178 p.Arg504His (c.1511G>A)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

CCDC178 p.Arg504His

c.1511G>A · rs140513669 · VCV2380668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -0.54
Regional constraint	o/e 1.04	unconstrained · MANE · 474 kb · p 0.17 · regional, not allelic
Overall
CADD	5.105	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0362% African / African-American · 27/74,576 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.022%

Overall 0.00435% 70/1,608,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0362%	2,762
Middle Eastern	0.0165%	6,052
South Asian	0.0155%	6,436
Remaining individualsnot grpmax-eligible	0.00802%	12,461
Admixed American	0.00505%	19,795
East Asian	0.00448%	22,316
European (non-Finnish)	0.00153%	65,427

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.Arg504His
Coding: c.1511G>A
MANE Select: NM_001105528
dbSNP: rs140513669
Type: single nucleotide variant
Location: chr18:33245327 (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-arg504his (accessed [today's date]).

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