Is CERS2 p.Arg13His (c.38G>A) pathogenic?

CERS2 p.Arg13His (c.38G>A) is classified Uncertain significance in CERS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). AlphaMissense: likely benign (0.125); Ultra-rare (popmax 0.0111%, eas).

How common is CERS2 p.Arg13His (c.38G>A) in the general population?

CERS2 p.Arg13His (c.38G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CERS2 p.Arg13His (c.38G>A)?

AlphaMissense predicts likely benign (score 0.125) — an in-silico prediction, not a clinical call.

CERS2 p.Arg13His

c.38G>A · rs587718634 · VCV2508560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.125 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.125	likely benign
REVEL	0.587	indeterminate
SaProt	LLR -8.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 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	25.4	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 0.0111% East Asian · 5/44,878 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000991% 16/1,614,050 alleles · ultra-rare exomes 14/1,461,834 · genomes 2/152,216 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,976
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
South Asian	0.00329%	30,361
Admixed American	0.00167%	60,008
European (non-Finnish)	0.000508%	196,672

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.Arg13His
Coding: c.38G>A
MANE Select: NM_022075
dbSNP: rs587718634
Type: single nucleotide variant
Location: chr1:150969053 (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.Arg13Pro 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-arg13his (accessed [today's date]).

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