Is CERS5 p.Val344Ala (c.1031T>C) pathogenic?

CERS5 p.Val344Ala (c.1031T>C) is classified Uncertain significance in CERS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). AlphaMissense: likely pathogenic (0.7566); Absent from gnomAD v4.1.

How common is CERS5 p.Val344Ala (c.1031T>C) in the general population?

CERS5 p.Val344Ala (c.1031T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERS5 p.Val344Ala (c.1031T>C)?

AlphaMissense predicts likely pathogenic (score 0.7566) — an in-silico prediction, not a clinical call.

CERS5 p.Val344Ala

c.1031T>C · rs2539572418 · VCV3143173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7566 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,582,700)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7566	likely pathogenic
REVEL	0.214	benign-leaning
SaProt	LLR -8.61	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 3,988 bp · p 1.9e-05 · regional, not allelic
Overall
CADD	28.3	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

No allele count reported in gnomAD v4.1 (AN 1,582,700). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CERS5
Protein: p.Val344Ala
Coding: c.1031T>C
MANE Select: NM_147190
dbSNP: rs2539572418
Type: single nucleotide variant
Location: chr12:50130693 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.91

Full CERS5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS5 p.Ala278Val Uncertain significance ★ ⚠ same type
CERS5 p.Ala2Thr Uncertain significance ★ ⚠ same type
CERS5 p.Ala338Ser Uncertain significance ★ ⚠ same type
CERS5 p.Ala377Thr Uncertain significance ★ ⚠ same type
CERS5 p.Arg127His Uncertain significance ★ ⚠ same type
CERS5 p.Arg238Gln Uncertain significance ★ ⚠ same type
CERS5 p.Arg267Gln Uncertain significance ★ ⚠ same type
CERS5 p.Arg284Gln 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/cers5-p-val344ala (accessed [today's date]).

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