Is CCS p.Leu93= (c.279G>T) pathogenic?

CCS p.Leu93= (c.279G>T) is classified Likely benign in CCS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-02). Low-frequency (popmax 1.25%, nfe); Associated with CCS-related disorder.

What condition is associated with CCS p.Leu93= (c.279G>T)?

CCS p.Leu93= (c.279G>T) is associated with CCS-related disorder (ClinVar).

How common is CCS p.Leu93= (c.279G>T) in the general population?

CCS p.Leu93= (c.279G>T) is low-frequency (popmax 1.25%, nfe) (gnomAD).

CCS p.Leu93=

c.279G>T · rs61731811 · VCV3041567

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.25%, nfe)

Conditions

CCS-related disorder

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 -0.98	GERP -4.8
Overall
CADD	0.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.25% European (non-Finnish) · 14,406/1,150,356 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.23%

Overall 1.03% 15,870/1,546,340 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.25%	80
Finnishnot grpmax-eligible	0.818%	122
Remaining individualsnot grpmax-eligible	0.775%	129
Admixed American	0.468%	214
South Asian	0.183%	546
African / African-American	0.169%	593
Middle Eastern	0.115%	868
Amishnot grpmax-eligible	0.11%	912
Ashkenazi Jewishnot grpmax-eligible	0.00386%	25,936
East Asian	0.00231%	43,376

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: CCS
Protein: p.Leu93=
Coding: c.279G>T
MANE Select: NM_005125
dbSNP: rs61731811
Type: single nucleotide variant
Location: chr11:66599487 (GRCh38)
Gene constraint: LOEUF 1.193 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.54 · 7 PDB
Residue 93: the 'superoxide dismutase-like' region; a β-strand

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

Disease context

CCS-related disorder

Similar variants

CCS p.Ala268= Benign same condition
CCS c.567+1G>C Uncertain significance ★ same type
CCS p.Ala173Thr Uncertain significance ★ ⚠ same type
CCS p.Ala179Thr Uncertain significance ★ ⚠ same type
CCS p.Ala234Thr Uncertain significance ★ ⚠ same type
CCS p.Ala260Ser Uncertain significance ★ ⚠ same type
CCS p.Ala260Thr Uncertain significance ★ ⚠ same type
CCS p.Arg163Gln 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/ccs-p-leu93 (accessed [today's date]).

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