Is CCDC50 p.Lys394Arg (c.1181A>G) pathogenic?

CCDC50 p.Lys394Arg (c.1181A>G) is classified Benign in CCDC50 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-28). AlphaMissense: likely benign (0.073); Low-frequency (popmax 2.56%, sas).

How common is CCDC50 p.Lys394Arg (c.1181A>G) in the general population?

CCDC50 p.Lys394Arg (c.1181A>G) is low-frequency (popmax 2.56%, sas) (gnomAD).

What do computational predictors say about CCDC50 p.Lys394Arg (c.1181A>G)?

AlphaMissense predicts likely benign (score 0.073) — an in-silico prediction, not a clinical call.

CCDC50 p.Lys394Arg

c.1181A>G · rs114502673 · VCV162860

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.073 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.56%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.073	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -7.82	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 5.3	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 62 kb · p 0.39 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM K218R vs ClinVar K394R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.56% South Asian · 2,332/91,054 alleles

Filtering AF 2.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.44%

Overall 0.623% 10,054/1,613,084 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.56%	39
Middle Eastern	1.04%	96
Amishnot grpmax-eligible	0.658%	152
Remaining individualsnot grpmax-eligible	0.645%	155
European (non-Finnish)	0.585%	171
Ashkenazi Jewishnot grpmax-eligible	0.565%	177
Admixed American	0.162%	617
African / African-American	0.0813%	1,229
Finnishnot grpmax-eligible	0.039%	2,561
East Asian	0.0112%	8,968

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: CCDC50
Protein: p.Lys394Arg
Coding: c.1181A>G
MANE Select: NM_178335
dbSNP: rs114502673
Type: single nucleotide variant
Location: chr3:191380871 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90 · 1 PDB

Full CCDC50 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC50 p.Ala453Val Uncertain significance ★★ ⚠ same type
CCDC50 p.Arg138Pro Uncertain significance ★★ ⚠ same type
CCDC50 p.Arg227Gln Uncertain significance ★★ same type
CCDC50 p.Arg227Trp Uncertain significance ★★ same type
CCDC50 p.Arg270Ter Uncertain significance ★★ same type
CCDC50 p.Arg274Ter Uncertain significance ★★ same type
CCDC50 p.Arg305Thr Uncertain significance ★★ same type
CCDC50 p.Arg309Gly 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/ccdc50-p-lys394arg (accessed [today's date]).

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