Is CCDC110 p.Ser346Arg (c.1038T>G) pathogenic?

CCDC110 p.Ser346Arg (c.1038T>G) is classified Uncertain significance in CCDC110 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.4281); Very rare (popmax 0.00133%, afr).

How common is CCDC110 p.Ser346Arg (c.1038T>G) in the general population?

CCDC110 p.Ser346Arg (c.1038T>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CCDC110 p.Ser346Arg (c.1038T>G)?

AlphaMissense predicts ambiguous (score 0.4281) — an in-silico prediction, not a clinical call.

CCDC110 p.Ser346Arg

c.1038T>G · VCV4648927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4281	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -7.20	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.95, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 26 kb · p 0.015 · regional, not allelic
Overall
CADD	19.1	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 0.00133% African / African-American · 1/74,936 alleles

Overall 6.85e-05% 1/1,460,630 alleles · very rare

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: CCDC110
Protein: p.Ser346Arg
Coding: c.1038T>G
MANE Select: NM_152775
Type: single nucleotide variant
Location: chr4:185459549 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.67

Full CCDC110 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC110 p.Ala207Thr Uncertain significance ★ ⚠ same type
CCDC110 p.Ala654Ser Uncertain significance ★ ⚠ same type
CCDC110 p.Ala68Asp Uncertain significance ★ ⚠ same type
CCDC110 p.Ala816Pro Uncertain significance ★ ⚠ same type
CCDC110 p.Arg202Cys Uncertain significance ★ ⚠ same type
CCDC110 p.Arg566Gln Uncertain significance ★ ⚠ same type
CCDC110 p.Arg566Gly Uncertain significance ★ ⚠ same type
CCDC110 p.Arg660Lys 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/ccdc110-p-ser346arg (accessed [today's date]).

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