Is CCDC85C p.Pro344Ser (c.1030C>T) pathogenic?

CCDC85C p.Pro344Ser (c.1030C>T) is classified Likely benign in CCDC85C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.0518); Ultra-rare (popmax 0.0107%, sas).

How common is CCDC85C p.Pro344Ser (c.1030C>T) in the general population?

CCDC85C p.Pro344Ser (c.1030C>T) is ultra-rare (popmax 0.0107%, sas) (gnomAD).

What do computational predictors say about CCDC85C p.Pro344Ser (c.1030C>T)?

AlphaMissense predicts likely benign (score 0.0518) — an in-silico prediction, not a clinical call.

CCDC85C p.Pro344Ser

c.1030C>T · VCV4221657

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0518 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0518	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -6.50	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 -2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 88 kb · p 0.57 · regional, not allelic
Overall
CADD	12.28	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 0.0107% South Asian · 9/84,064 alleles

Filtering AF 0.00552% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00413%

Overall 0.000968% 15/1,550,272 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0107%	9,340
Admixed American	0.00785%	12,738
European (non-Finnish)	0.000174%	573,437

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: CCDC85C
Protein: p.Pro344Ser
Coding: c.1030C>T
MANE Select: NM_001144995
Type: single nucleotide variant
Location: chr14:99517129 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.38
Residue 344: the 'disordered' region

Full CCDC85C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNK p.Pro462Thr Uncertain significance ★★ ⚠ same type
CCNK p.Val333Phe Uncertain significance ★★ ⚠ same type
CCNK p.Pro484= Likely benign ★★ same type
CCDC85C p.Ala102Val Uncertain significance ★ ⚠ same type
CCDC85C p.Ala11Ser Uncertain significance ★ ⚠ same type
CCDC85C p.Ala156Thr Uncertain significance ★ ⚠ same type
CCDC85C p.Ala156Val Uncertain significance ★ ⚠ same type
CCDC85C p.Ala157Val 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/ccdc85c-p-pro344ser (accessed [today's date]).

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