Is CCDC85A p.Pro438Ser (c.1312C>T) pathogenic?

CCDC85A p.Pro438Ser (c.1312C>T) is classified Uncertain significance in CCDC85A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: ambiguous (0.3808); Ultra-rare (popmax 0.014%, amr).

How common is CCDC85A p.Pro438Ser (c.1312C>T) in the general population?

CCDC85A p.Pro438Ser (c.1312C>T) is ultra-rare (popmax 0.014%, amr) (gnomAD).

What do computational predictors say about CCDC85A p.Pro438Ser (c.1312C>T)?

AlphaMissense predicts ambiguous (score 0.3808) — an in-silico prediction, not a clinical call.

CCDC85A p.Pro438Ser

c.1312C>T · VCV3997250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3808 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3808	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 200 kb · p 0.0042 · regional, not allelic
Overall
CADD	23.5	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 0.014% Admixed American · 8/57,142 alleles

Filtering AF 0.0069% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00503%

Overall 0.00164% 26/1,589,966 alleles · ultra-rare exomes 23/1,437,788 · genomes 3/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.014%	7,143
Remaining individualsnot grpmax-eligible	0.00325%	30,784
African / African-American	0.00269%	37,174
Finnishnot grpmax-eligible	0.00159%	62,710
South Asian	0.00114%	87,418
European (non-Finnish)	0.00103%	97,234

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: CCDC85A
Protein: p.Pro438Ser
Coding: c.1312C>T
MANE Select: NM_001080433
Type: single nucleotide variant
Location: chr2:56342950 (GRCh38)
Gene constraint: LOEUF 1.058 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.16
Residue 438: the 'disordered' region

Full CCDC85A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC85A p.Ala13Val Uncertain significance ★ ⚠ same type
CCDC85A p.Ala142Ser Uncertain significance ★ ⚠ same type
CCDC85A p.Ala178Val Uncertain significance ★ ⚠ same type
CCDC85A p.Ala201Pro Uncertain significance ★ ⚠ same type
CCDC85A p.Ala201Val Uncertain significance ★ ⚠ same type
CCDC85A p.Ala21Ser Uncertain significance ★ ⚠ same type
CCDC85A p.Ala21Val Uncertain significance ★ ⚠ same type
CCDC85A p.Ala28Asp 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/ccdc85a-p-pro438ser (accessed [today's date]).

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