Is CERS2 p.Arg31Ser (c.91C>A) pathogenic?

CERS2 p.Arg31Ser (c.91C>A) is classified Uncertain significance in CERS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-13). AlphaMissense: ambiguous (0.5423); Very rare (popmax 8.47e-05%, nfe).

How common is CERS2 p.Arg31Ser (c.91C>A) in the general population?

CERS2 p.Arg31Ser (c.91C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CERS2 p.Arg31Ser (c.91C>A)?

AlphaMissense predicts ambiguous (score 0.5423) — an in-silico prediction, not a clinical call.

CERS2 p.Arg31Ser

c.91C>A · rs140031607 · VCV2266327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5423 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5423	ambiguous
REVEL	0.339	indeterminate
SaProt	LLR -8.95	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 1,991 bp · p 3.1e-05 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,984 alleles

Overall 6.2e-05% 1/1,614,068 alleles · very rare exomes 1/1,461,792 · genomes 0/152,276 · joint denominator

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.Arg31Ser
Coding: c.91C>A
MANE Select: NM_022075
dbSNP: rs140031607
Type: single nucleotide variant
Location: chr1:150969000 (GRCh38)
Gene constraint: LOEUF 0.501 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 87.31

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

Similar variants

CERS2 p.Arg31His Uncertain significance ★ ⚠ same residue
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

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-arg31ser (accessed [today's date]).

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