Is CERS6 p.Ala362Val (c.1085C>T) pathogenic?

CERS6 p.Ala362Val (c.1085C>T) is classified Uncertain significance in CERS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0768); Ultra-rare (popmax 0.0218%, amr).

How common is CERS6 p.Ala362Val (c.1085C>T) in the general population?

CERS6 p.Ala362Val (c.1085C>T) is ultra-rare (popmax 0.0218%, amr) (gnomAD).

What do computational predictors say about CERS6 p.Ala362Val (c.1085C>T)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

CERS6 p.Ala362Val

c.1085C>T · VCV4652667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0218%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.11, phastCons 0.24
Regional constraint	o/e 0.89	unconstrained · MANE · 313 kb · p 0.015 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0218% Admixed American · 13/59,620 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.00136% 22/1,612,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0218%	4,586
Remaining individualsnot grpmax-eligible	0.00481%	20,811
East Asian	0.00223%	44,814
Finnishnot grpmax-eligible	0.00156%	64,014
European (non-Finnish)	0.000339%	294,863

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: CERS6
Protein: p.Ala362Val
Coding: c.1085C>T
MANE Select: NM_203463
Type: single nucleotide variant
Location: chr2:168769592 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 87.97 · 3 PDB
Residue 362: the 'disordered' region

Full CERS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS6 p.Ala30Ser Uncertain significance ★ ⚠ same type
CERS6 p.Ala326Val Uncertain significance ★ ⚠ same type
CERS6 p.Ala6Val Uncertain significance ★ ⚠ same type
CERS6 p.Arg121Cys Uncertain significance ★ ⚠ same type
CERS6 p.Asn10Lys Uncertain significance ★ ⚠ same type
CERS6 p.Asn122Ser Uncertain significance ★ ⚠ same type
CERS6 p.Asn168Lys Uncertain significance ★ same type
CERS6 p.Asn18Ser 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/cers6-p-ala362val (accessed [today's date]).

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