Is CCDC15 p.Met248Val (c.742A>G) pathogenic?

CCDC15 p.Met248Val (c.742A>G) is classified Uncertain significance in CCDC15 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-26). AlphaMissense: likely benign (0.1206); Very rare (popmax 0.00516%, amr).

How common is CCDC15 p.Met248Val (c.742A>G) in the general population?

CCDC15 p.Met248Val (c.742A>G) is very rare (popmax 0.00516%, amr) (gnomAD).

What do computational predictors say about CCDC15 p.Met248Val (c.742A>G)?

AlphaMissense predicts likely benign (score 0.1206) — an in-silico prediction, not a clinical call.

CCDC15 p.Met248Val

c.742A>G · rs758389024 · VCV2600861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00516%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1206	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.60	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 0.61	GERP -0.82, phastCons 0.002
Regional constraint	o/e 1.01	unconstrained · MANE · 86 kb · p 0.73 · regional, not allelic
Overall
CADD	6.128	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 0.00516% Admixed American · 3/58,120 alleles

Filtering AF 0.00137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00068%

Overall 0.000624% 10/1,602,658 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00516%	19,373
African / African-American	0.00135%	74,190
European (non-Finnish)	0.00051%	195,896

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: CCDC15
Protein: p.Met248Val
Coding: c.742A>G
MANE Select: NM_025004
dbSNP: rs758389024
Type: single nucleotide variant
Location: chr11:124977589 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.02

Full CCDC15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC15 p.Arg181Cys Uncertain significance ★★ ⚠ same type
CCDC15 p.Pro10= Benign ★★ same type
CCDC15 p.Ala110Thr Uncertain significance ★ ⚠ same type
CCDC15 p.Ala140Val Uncertain significance ★ ⚠ same type
CCDC15 p.Ala19Thr Uncertain significance ★ ⚠ same type
CCDC15 p.Ala44Ser Uncertain significance ★ ⚠ same type
CCDC15 p.Ala44Val Uncertain significance ★ ⚠ same type
CCDC15 p.Ala6Thr 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/ccdc15-p-met248val (accessed [today's date]).

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