Is CERS2 p.Val267Ile (c.799G>A) pathogenic?

CERS2 p.Val267Ile (c.799G>A) is classified Likely benign in CERS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). AlphaMissense: likely benign (0.0796); Rare (popmax 0.656%, nfe).

How common is CERS2 p.Val267Ile (c.799G>A) in the general population?

CERS2 p.Val267Ile (c.799G>A) is rare (popmax 0.656%, nfe) (gnomAD).

What do computational predictors say about CERS2 p.Val267Ile (c.799G>A)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

CERS2 p.Val267Ile

c.799G>A · rs149992226 · VCV2639166

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.656%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -6.78	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 -0.52	GERP -3.9
Regional constraint	o/e 0.80	unconstrained · MANE · 670 bp · p 0.015 · regional, not allelic
Overall
CADD	2.804	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 0.656% European (non-Finnish) · 7,739/1,179,970 alleles

Filtering AF 0.644% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.639%

Overall 0.557% 8,986/1,614,048 alleles · rare exomes 8,369/1,461,818 · genomes 617/152,230 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.1%	91
Finnishnot grpmax-eligible	0.87%	115
European (non-Finnish)grpmax	0.656%	152
Remaining individualsnot grpmax-eligible	0.557%	180
Middle Eastern	0.479%	209
Admixed American	0.228%	438
African / African-American	0.096%	1,042
South Asian	0.0812%	1,231
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,558
East Asian	0.00223%	44,888

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: CERS2
Protein: p.Val267Ile
Coding: c.799G>A
MANE Select: NM_022075
dbSNP: rs149992226
Type: single nucleotide variant
Location: chr1:150966805 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 87.31
Residue 267: the tlc domain

Full CERS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS2 p.Ala152= Benign ★★ same type
CERS2 p.Ser199= Benign ★★ same type
CERS2 p.Tyr254= Benign ★★ same type
CERS2 p.Ala23Ser Uncertain significance ★ ⚠ same type
CERS2 p.Ala23Val Uncertain significance ★ ⚠ same type
CERS2 p.Ala34Thr Uncertain significance ★ same type
CERS2 p.Ala46Gly Uncertain significance ★ ⚠ same type
CERS2 p.Arg105Leu 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/cers2-p-val267ile (accessed [today's date]).

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