Is CERS6 p.Ala6Val (c.17C>T) pathogenic?

CERS6 p.Ala6Val (c.17C>T) is classified Uncertain significance in CERS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.6897); Ultra-rare (popmax 0.0198%, nfe).

How common is CERS6 p.Ala6Val (c.17C>T) in the general population?

CERS6 p.Ala6Val (c.17C>T) is ultra-rare (popmax 0.0198%, nfe) (gnomAD).

What do computational predictors say about CERS6 p.Ala6Val (c.17C>T)?

AlphaMissense predicts likely pathogenic (score 0.6897) — an in-silico prediction, not a clinical call.

CERS6 p.Ala6Val

c.17C>T · VCV3491057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6897 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6897	likely pathogenic
REVEL	0.066	moderately benign-leaning
SaProt	LLR -9.46	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 313 kb · p 0.015 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 0.0198% European (non-Finnish) · 234/1,179,666 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0169%

Overall 0.0148% 239/1,613,594 alleles · ultra-rare exomes 229/1,461,408 · genomes 10/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0198%	5,041
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0048%	20,825
African / African-American	0.00133%	74,992

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.Ala6Val
Coding: c.17C>T
MANE Select: NM_203463
Type: single nucleotide variant
Location: chr2:168456465 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 87.97 · 3 PDB
Residue 6: an α-helix

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.Ala362Val 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-ala6val (accessed [today's date]).

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