Is CCDC110 p.Met557Ile (c.1671G>T) pathogenic?

CCDC110 p.Met557Ile (c.1671G>T) is classified Uncertain significance in CCDC110 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-14). AlphaMissense: ambiguous (0.3903); Ultra-rare (popmax 0.0313%, eas).

How common is CCDC110 p.Met557Ile (c.1671G>T) in the general population?

CCDC110 p.Met557Ile (c.1671G>T) is ultra-rare (popmax 0.0313%, eas) (gnomAD).

What do computational predictors say about CCDC110 p.Met557Ile (c.1671G>T)?

AlphaMissense predicts ambiguous (score 0.3903) — an in-silico prediction, not a clinical call.

CCDC110 p.Met557Ile

c.1671G>T · rs368029395 · VCV2599067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3903 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0313%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3903	ambiguous
REVEL	0.093	moderately benign-leaning
SaProt	LLR -5.21	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 1.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 26 kb · p 0.015 · regional, not allelic
Overall
CADD	15.65	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 0.0313% East Asian · 14/44,670 alleles

Filtering AF 0.0203% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0173%

Overall 0.00329% 53/1,608,958 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0313%	3,191
South Asian	0.0289%	3,455
Remaining individualsnot grpmax-eligible	0.016%	6,235
European (non-Finnish)	0.000254%	392,933

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.Met557Ile
Coding: c.1671G>T
MANE Select: NM_152775
dbSNP: rs368029395
Type: single nucleotide variant
Location: chr4:185458916 (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.Met557Thr Uncertain significance ★ ⚠ same residue
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

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-met557ile (accessed [today's date]).

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