Is CCDC121 p.Val260Ile (c.778G>A) pathogenic?

CCDC121 p.Val260Ile (c.778G>A) is classified Uncertain significance in CCDC121 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely benign (0.0871); Ultra-rare (popmax 0.02%, eas).

How common is CCDC121 p.Val260Ile (c.778G>A) in the general population?

CCDC121 p.Val260Ile (c.778G>A) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about CCDC121 p.Val260Ile (c.778G>A)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

CCDC121 p.Val260Ile

c.778G>A · rs756637183 · VCV3138299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.23	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 0.017	GERP 1
Regional constraint	o/e 0.78	unconstrained · MANE · 833 bp · p 0.00015 · regional, not allelic
Overall
CADD	9.621	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 0.02% East Asian · 9/44,890 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000867% 14/1,613,900 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
Remaining individualsnot grpmax-eligible	0.0032%	31,239
Admixed American	0.00167%	59,936
African / African-American	0.00133%	74,944
European (non-Finnish)	8.47e-05%	1,179,972

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: CCDC121
Protein: p.Val260Ile
Coding: c.778G>A
MANE Select: NM_024584
dbSNP: rs756637183
Type: single nucleotide variant
Location: chr2:27627022 (GRCh38)
Gene constraint: LOEUF 1.848 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 87.88
Residue 260: the 'disordered' region

Full CCDC121 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC121 c.-116T>C Uncertain significance ★ same type
CCDC121 c.-119+251C>T Uncertain significance ★ same type
CCDC121 c.-119+257G>A Uncertain significance ★ same type
CCDC121 c.-119+287C>T Uncertain significance ★ same type
CCDC121 c.-119+292C>G Uncertain significance ★ same type
CCDC121 c.-119+298T>C Uncertain significance ★ same type
CCDC121 c.-119+337C>A Uncertain significance ★ same type
CCDC121 c.-119+385C>G 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/ccdc121-p-val260ile (accessed [today's date]).

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