Is CERS4 p.Phe273Ser (c.818T>C) pathogenic?

CERS4 p.Phe273Ser (c.818T>C) is classified Uncertain significance in CERS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: ambiguous (0.4099); Absent from gnomAD v4.1.

How common is CERS4 p.Phe273Ser (c.818T>C) in the general population?

CERS4 p.Phe273Ser (c.818T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERS4 p.Phe273Ser (c.818T>C)?

AlphaMissense predicts ambiguous (score 0.4099) — an in-silico prediction, not a clinical call.

CERS4 p.Phe273Ser

c.818T>C · rs2512553428 · VCV2260711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4099 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4099	ambiguous
REVEL	0.758	pathogenic-leaning
SaProt	LLR -8.55	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 11 kb · p 0.0051 · regional, not allelic
Overall
CADD	24.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CERS4
Protein: p.Phe273Ser
Coding: c.818T>C
MANE Select: NM_024552
dbSNP: rs2512553428
Type: single nucleotide variant
Location: chr19:8257955 (GRCh38)
Gene constraint: LOEUF 1.472 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.92
Residue 273: the tlc domain

Full CERS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS4 p.Ala82Thr Likely benign ★★ same type
CERS4 p.Leu194= Benign ★★ same type
CERS4 p.Ala162Val Uncertain significance ★ ⚠ same type
CERS4 p.Ala373Thr Uncertain significance ★ ⚠ same type
CERS4 p.Ala46Val Uncertain significance ★ ⚠ same type
CERS4 p.Arg116Gln Uncertain significance ★ ⚠ same type
CERS4 p.Arg121His Uncertain significance ★ ⚠ same type
CERS4 p.Arg203Cys 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/cers4-p-phe273ser (accessed [today's date]).

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