Is CCDC38 p.Lys414Arg (c.1241A>G) pathogenic?

CCDC38 p.Lys414Arg (c.1241A>G) is classified Likely benign in CCDC38 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.0615); Ultra-rare (popmax 0.0312%, eas).

How common is CCDC38 p.Lys414Arg (c.1241A>G) in the general population?

CCDC38 p.Lys414Arg (c.1241A>G) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about CCDC38 p.Lys414Arg (c.1241A>G)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

CCDC38 p.Lys414Arg

c.1241A>G · rs750316596 · VCV3139128

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.9	GERP 0.81, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.61 · regional, not allelic
Overall
CADD	13.07	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,836 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00118% 19/1,613,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,203
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)	0.000254%	393,275

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: CCDC38
Protein: p.Lys414Arg
Coding: c.1241A>G
MANE Select: NM_182496
dbSNP: rs750316596
Type: single nucleotide variant
Location: chr12:95878248 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.84

Full CCDC38 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC38 p.Ala125Ser Uncertain significance ★ ⚠ same type
CCDC38 p.Ala175Ser Uncertain significance ★ ⚠ same type
CCDC38 p.Ala175Thr Uncertain significance ★ ⚠ same type
CCDC38 p.Ala407Val Uncertain significance ★ ⚠ same type
CCDC38 p.Ala425Val Uncertain significance ★ ⚠ same type
CCDC38 p.Ala76Pro Uncertain significance ★ ⚠ same type
CCDC38 p.Arg107Met Uncertain significance ★ ⚠ same type
CCDC38 p.Arg145Gln 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/ccdc38-p-lys414arg (accessed [today's date]).

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