Is CCDC88A p.Lys891Met (c.2672A>T) pathogenic?

CCDC88A p.Lys891Met (c.2672A>T) is classified Uncertain significance in CCDC88A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-27). AlphaMissense: likely pathogenic (0.7091); Very rare (popmax 0.000192%, nfe).

How common is CCDC88A p.Lys891Met (c.2672A>T) in the general population?

CCDC88A p.Lys891Met (c.2672A>T) is very rare (popmax 0.000192%, nfe) (gnomAD).

What do computational predictors say about CCDC88A p.Lys891Met (c.2672A>T)?

AlphaMissense predicts likely pathogenic (score 0.7091) — an in-silico prediction, not a clinical call.

CCDC88A p.Lys891Met

c.2672A>T · rs2544835002 · VCV1958224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000192%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7091	likely pathogenic
REVEL	0.232	benign-leaning
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 62 kb · p 2.8e-11 · regional, not allelic
Overall
CADD	26.4	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 0.000192% European (non-Finnish) · 2/1,042,862 alleles

Filtering AF 3.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000149% 2/1,345,236 alleles · very rare exomes 2/1,193,086 · genomes 0/152,150 · joint denominator

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: CCDC88A
Protein: p.Lys891Met
Coding: c.2672A>T
MANE Select: NM_001365480
dbSNP: rs2544835002
Type: single nucleotide variant
Location: chr2:55334149 (GRCh38)
Gene constraint: LOEUF 0.25 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.09 · 1 PDB

Full CCDC88A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC88A p.Lys891= Likely benign ★ same residue
CCDC88A p.Ala1536Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala155Val Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala158Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala1770Val Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala194Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala72Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala845Gly 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/ccdc88a-p-lys891met (accessed [today's date]).

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