Is CSE1L p.Asn537Ser (c.1610A>G) pathogenic?

CSE1L p.Asn537Ser (c.1610A>G) is classified Uncertain significance in CSE1L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0702); Ultra-rare (popmax 0.0296%, sas).

How common is CSE1L p.Asn537Ser (c.1610A>G) in the general population?

CSE1L p.Asn537Ser (c.1610A>G) is ultra-rare (popmax 0.0296%, sas) (gnomAD).

What do computational predictors say about CSE1L p.Asn537Ser (c.1610A>G)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

CSE1L p.Asn537Ser

c.1610A>G · VCV4234782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.08	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 1.3	GERP -3.2, phastCons 0.1
Regional constraint	o/e 0.85	unconstrained · MANE · 27 kb · p 0.00012 · regional, not allelic
Overall
CADD	12.84	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 0.0296% South Asian · 27/91,064 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00335% 54/1,613,876 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0296%	3,373
East Asian	0.00668%	14,962
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.00186%	53,633

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: CSE1L
Protein: p.Asn537Ser
Coding: c.1610A>G
MANE Select: NM_001316
Type: single nucleotide variant
Location: chr20:49084153 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.22

Full CSE1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSE1L p.Ala179Ser Uncertain significance ★ ⚠ same type
CSE1L p.Ala190Val Uncertain significance ★ ⚠ same type
CSE1L p.Ala417Thr Uncertain significance ★ ⚠ same type
CSE1L p.Ala438Ser Uncertain significance ★ same type
CSE1L p.Ala513Thr Uncertain significance ★ same type
CSE1L p.Ala543Val Uncertain significance ★ ⚠ same type
CSE1L p.Ala547Val Uncertain significance ★ ⚠ same type
CSE1L p.Arg137His 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/cse1l-p-asn537ser (accessed [today's date]).

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