Is CCDC185 p.Ser96Phe (c.287C>T) pathogenic?

CCDC185 p.Ser96Phe (c.287C>T) is classified Uncertain significance in CCDC185 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely benign (0.1995); Ultra-rare (popmax 0.0215%, eas).

How common is CCDC185 p.Ser96Phe (c.287C>T) in the general population?

CCDC185 p.Ser96Phe (c.287C>T) is ultra-rare (popmax 0.0215%, eas) (gnomAD).

What do computational predictors say about CCDC185 p.Ser96Phe (c.287C>T)?

AlphaMissense predicts likely benign (score 0.1995) — an in-silico prediction, not a clinical call.

CCDC185 p.Ser96Phe

c.287C>T · rs768406969 · VCV3138998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1995 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0215%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1995	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -8.80	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 0.76	GERP 0.33
Regional constraint	o/e 1.19	unconstrained · MANE · 1,868 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	16.9	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 0.0215% East Asian · 9/41,956 alleles

Filtering AF 0.0111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00826%

Overall 0.000703% 11/1,564,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0215%	4,662
Ashkenazi Jewishnot grpmax-eligible	0.00347%	28,798
European (non-Finnish)	8.64e-05%	1,157,156

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: CCDC185
Protein: p.Ser96Phe
Coding: c.287C>T
MANE Select: NM_152610
dbSNP: rs768406969
Type: single nucleotide variant
Location: chr1:223393762 (GRCh38)
Gene constraint: LOEUF 1.695 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 69.31
Residue 96: the 'disordered' region

Full CCDC185 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC185 p.Ala364Val Uncertain significance ★ ⚠ same type
CCDC185 p.Ala404Thr Uncertain significance ★ ⚠ same type
CCDC185 p.Ala432Gly Uncertain significance ★ ⚠ same type
CCDC185 p.Ala441Ser Uncertain significance ★ ⚠ same type
CCDC185 p.Ala441Thr Uncertain significance ★ ⚠ same type
CCDC185 p.Ala510Val Uncertain significance ★ ⚠ same type
CCDC185 p.Ala55Val Uncertain significance ★ ⚠ same type
CCDC185 p.Ala564Thr 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/ccdc185-p-ser96phe (accessed [today's date]).

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