Is CERS3 p.Leu308= (c.924C>T) pathogenic?

CERS3 p.Leu308= (c.924C>T) is classified Likely benign in CERS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). Ultra-rare (popmax 0.0314%, nfe).

How common is CERS3 p.Leu308= (c.924C>T) in the general population?

CERS3 p.Leu308= (c.924C>T) is ultra-rare (popmax 0.0314%, nfe) (gnomAD).

CERS3 p.Leu308=

c.924C>T · VCV4740929

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0314%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Pangolin	Δ0.20	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.7	GERP 0.13, phastCons 1
Overall
CADD	14.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0314% European (non-Finnish) · 370/1,178,854 alleles

Filtering AF 0.0287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0277%

Overall 0.0239% 386/1,612,542 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.329%	304
European (non-Finnish)grpmax	0.0314%	3,186
Remaining individualsnot grpmax-eligible	0.00961%	10,407
African / African-American	0.00801%	12,479
Admixed American	0.00167%	59,936

Amish 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: CERS3
Protein: p.Leu308=
Coding: c.924C>T
MANE Select: NM_001378789
Type: single nucleotide variant
Location: chr15:100455968 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.52
Residue 308: the tlc domain

Full CERS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS3 c.466-1G>T Likely pathogenic ★★ same type
CERS3 p.Arg75Ter Likely pathogenic ★★ same type
CERS3 p.Arg275Cys Uncertain significance ★★ ⚠ same type
CERS3 p.Ser177Phe Uncertain significance ★★ ⚠ same type
CERS3 c.174-81G>A Benign ★★ same type
CERS3 c.407+74C>T Benign ★★ same type
CERS3 c.465+65A>T Benign ★★ same type
CERS3 c.466-110G>T Benign ★★ 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/cers3-p-leu308 (accessed [today's date]).

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