Is CCSER1 p.Arg596Gln (c.1787G>A) pathogenic?

CCSER1 p.Arg596Gln (c.1787G>A) is classified Uncertain significance in CCSER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0742); Ultra-rare (popmax 0.0132%, sas).

How common is CCSER1 p.Arg596Gln (c.1787G>A) in the general population?

CCSER1 p.Arg596Gln (c.1787G>A) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about CCSER1 p.Arg596Gln (c.1787G>A)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

CCSER1 p.Arg596Gln

c.1787G>A · VCV4222325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -5.64	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 2.1	GERP 1.6, phastCons 0.094
Regional constraint	o/e 1.05	unconstrained · MANE · 1,291 kb · p 0.093 · regional, not allelic
Overall
CADD	14.78	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 0.0132% South Asian · 12/91,064 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00211% 34/1,613,230 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,589
Admixed American	0.01%	9,992
Remaining individualsnot grpmax-eligible	0.0048%	20,813
East Asian	0.00223%	44,866
African / African-American	0.00134%	74,776
European (non-Finnish)	0.000932%	107,239

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: CCSER1
Protein: p.Arg596Gln
Coding: c.1787G>A
MANE Select: NM_001145065
Type: single nucleotide variant
Location: chr4:90628087 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 47.56

Full CCSER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCSER1 p.Val734Ala Benign ★★ same type
CCSER1 p.Ala238Val Uncertain significance ★ ⚠ same type
CCSER1 p.Ala353Val Uncertain significance ★ ⚠ same type
CCSER1 p.Ala357Thr Uncertain significance ★ ⚠ same type
CCSER1 p.Ala440Val Uncertain significance ★ ⚠ same type
CCSER1 p.Ala589Pro Uncertain significance ★ ⚠ same type
CCSER1 p.Ala707Pro Uncertain significance ★ ⚠ same type
CCSER1 p.Ala823Thr 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/ccser1-p-arg596gln (accessed [today's date]).

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