Is CCDC110 p.Val708Ala (c.2123T>C) pathogenic?

CCDC110 p.Val708Ala (c.2123T>C) is classified Uncertain significance in CCDC110 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: ambiguous (0.4994); Ultra-rare (popmax 0.036%, nfe).

How common is CCDC110 p.Val708Ala (c.2123T>C) in the general population?

CCDC110 p.Val708Ala (c.2123T>C) is ultra-rare (popmax 0.036%, nfe) (gnomAD).

What do computational predictors say about CCDC110 p.Val708Ala (c.2123T>C)?

AlphaMissense predicts ambiguous (score 0.4994) — an in-silico prediction, not a clinical call.

CCDC110 p.Val708Ala

c.2123T>C · rs140552849 · VCV2454959

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4994 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4994	ambiguous · top 9% in CCDC110
REVEL	0.05	moderately benign-leaning
SaProt	LLR -8.03	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 9.4	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 26 kb · p 0.015 · regional, not allelic
Overall
CADD	23.8	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 0.036% European (non-Finnish) · 424/1,176,164 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.0274% 438/1,600,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.036%	2,774
Remaining individualsnot grpmax-eligible	0.0161%	6,197
African / African-American	0.0027%	37,103
East Asian	0.00224%	44,672
Finnishnot grpmax-eligible	0.00158%	63,254

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.Val708Ala
Coding: c.2123T>C
MANE Select: NM_152775
dbSNP: rs140552849
Type: single nucleotide variant
Location: chr4:185458464 (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-val708ala (accessed [today's date]).

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