Is CCP110 p.Ser703Pro (c.2107T>C) pathogenic?

CCP110 p.Ser703Pro (c.2107T>C) is classified Uncertain significance in CCP110 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.0851); Very rare (popmax 0.00806%, nfe).

How common is CCP110 p.Ser703Pro (c.2107T>C) in the general population?

CCP110 p.Ser703Pro (c.2107T>C) is very rare (popmax 0.00806%, nfe) (gnomAD).

What do computational predictors say about CCP110 p.Ser703Pro (c.2107T>C)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

CCP110 p.Ser703Pro

c.2107T>C · VCV3997729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00806%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.86	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 1.2	GERP 0.38, phastCons 0.22
Overall
CADD	15.3	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 0.00806% European (non-Finnish) · 95/1,178,198 alleles

Filtering AF 0.00673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00625%

Overall 0.00609% 98/1,608,814 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00806%	12,402
Remaining individualsnot grpmax-eligible	0.00321%	31,126
African / African-American	0.00134%	74,604

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: CCP110
Protein: p.Ser703Pro
Coding: c.2107T>C
MANE Select: NM_001323572
Type: single nucleotide variant
Location: chr16:19541944 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.11

Full CCP110 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCP110 p.Ala433= Benign ★★ same type
CCP110 p.Arg845= Benign ★★ same type
CCP110 p.Asn740= Benign ★★ same type
CCP110 p.Ile252Met Benign ★★ same type
CCP110 p.Lys583= Benign ★★ same type
CCP110 p.Met375Ile Benign ★★ same type
CCP110 p.Pro171Leu Benign ★★ same type
CCP110 p.Thr122= Benign ★★ 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/ccp110-p-ser703pro (accessed [today's date]).

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