Is CCDC88A p.Leu79= (c.237A>G) pathogenic?

CCDC88A p.Leu79= (c.237A>G) is classified Benign/Likely benign in CCDC88A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). Rare (popmax 0.475%, mid).

How common is CCDC88A p.Leu79= (c.237A>G) in the general population?

CCDC88A p.Leu79= (c.237A>G) is rare (popmax 0.475%, mid) (gnomAD).

CCDC88A p.Leu79=

c.237A>G · rs147639776 · VCV781805

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.475%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -5.7
Overall
CADD	0.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.475% Middle Eastern · 28/5,900 alleles

Filtering AF 0.337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.291%

Overall 0.207% 3,169/1,533,236 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.23%	81
Middle Easterngrpmax	0.475%	211
Remaining individualsnot grpmax-eligible	0.225%	445
European (non-Finnish)	0.216%	464
Admixed American	0.148%	674
South Asian	0.0942%	1,062
Finnishnot grpmax-eligible	0.0723%	1,384
African / African-American	0.0388%	2,578
East Asian	0.00236%	42,378

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu79=
Coding: c.237A>G
MANE Select: NM_001365480
dbSNP: rs147639776
Type: single nucleotide variant
Location: chr2:55388814 (GRCh38)
Gene constraint: LOEUF 0.25 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.09 · 1 PDB
Residue 79: the calponin-homology (ch) domain

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

Similar variants

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
CCDC88A p.Arg1169His 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-leu79 (accessed [today's date]).

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