Is CCDC85C p.Ala11Ser (c.31G>T) pathogenic?

CCDC85C p.Ala11Ser (c.31G>T) is classified Uncertain significance in CCDC85C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.0737); Very rare (popmax 0.00751%, afr).

How common is CCDC85C p.Ala11Ser (c.31G>T) in the general population?

CCDC85C p.Ala11Ser (c.31G>T) is very rare (popmax 0.00751%, afr) (gnomAD).

What do computational predictors say about CCDC85C p.Ala11Ser (c.31G>T)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

CCDC85C p.Ala11Ser

c.31G>T · rs1281949461 · VCV3139484

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00751%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.74	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 0.98	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 597 bp · p 0.026 · regional, not allelic
Overall
CADD	18.35	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 0.00751% African / African-American · 5/66,548 alleles

Filtering AF 0.00289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00189%

Overall 0.00234% 33/1,413,072 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00751%	13,310
European (non-Finnish)	0.00248%	40,309
Remaining individualsnot grpmax-eligible	0.00185%	54,126

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.Ala11Ser
Coding: c.31G>T
MANE Select: NM_001144995
dbSNP: rs1281949461
Type: single nucleotide variant
Location: chr14:99603929 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.38

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.Ala156Thr Uncertain significance ★ ⚠ same type
CCDC85C p.Ala156Val Uncertain significance ★ ⚠ same type
CCDC85C p.Ala157Val Uncertain significance ★ ⚠ same type
CCDC85C p.Ala199Val 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-ala11ser (accessed [today's date]).

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