Is CCP110 p.Met375Ile (c.1125G>A) pathogenic?

CCP110 p.Met375Ile (c.1125G>A) is classified Benign in CCP110 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-03-28). AlphaMissense: likely benign (0.2444); Common (popmax 20.1%, mid) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CCP110 p.Met375Ile (c.1125G>A)?

AlphaMissense predicts likely benign (score 0.2444) — an in-silico prediction, not a clinical call.

CCP110 p.Met375Ile

Q: How common is CCP110 p.Met375Ile (c.1125G>A) in the general population?

CCP110 p.Met375Ile (c.1125G>A) is common (popmax 20.1%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1125G>A · rs7190666 · VCV402513

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2444 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 20.1%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2444	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -5.09	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 6.7	GERP 2, phastCons 1
Overall
CADD	23.2	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 20.1% Middle Eastern · 1,217/6,062 alleles

Filtering AF 19.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.8%

Overall 15% 242,154/1,613,874 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	20.2%	5
Middle Easterngrpmax	20.1%	5
Admixed American	19.1%	5
East Asian	17.8%	6
African / African-American	15.6%	6
Remaining individualsnot grpmax-eligible	15.4%	6
European (non-Finnish)	15.2%	7
Finnishnot grpmax-eligible	11.5%	9
Amishnot grpmax-eligible	10.7%	9
South Asian	8.57%	12

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met375Ile
Coding: c.1125G>A
MANE Select: NM_001323572
dbSNP: rs7190666
Type: single nucleotide variant
Location: chr16:19536794 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.11
Residue 375: a UniProt-annotated variant site (in); the 'interaction with cep76' region

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.Pro171Leu Benign ★★ same type
CCP110 p.Thr122= Benign ★★ same type
CCP110 p.Thr560Met 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-met375ile (accessed [today's date]).

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