Is CCSER1 p.Ile871Val (c.2611A>G) pathogenic?

CCSER1 p.Ile871Val (c.2611A>G) is classified Uncertain significance in CCSER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.171); Very rare (popmax 0.00119%, sas).

How common is CCSER1 p.Ile871Val (c.2611A>G) in the general population?

CCSER1 p.Ile871Val (c.2611A>G) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about CCSER1 p.Ile871Val (c.2611A>G)?

AlphaMissense predicts likely benign (score 0.171) — an in-silico prediction, not a clinical call.

CCSER1 p.Ile871Val

c.2611A>G · VCV4222348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.171 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.171	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -5.27	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,291 kb · p 0.093 · regional, not allelic
Overall
CADD	22.6	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 0.00119% South Asian · 1/84,058 alleles

Filtering AF 0.000632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000487%

Overall 0.001% 14/1,399,306 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	84,058
European (non-Finnish)	0.00113%	88,224

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.Ile871Val
Coding: c.2611A>G
MANE Select: NM_001145065
Type: single nucleotide variant
Location: chr4:91598965 (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-ile871val (accessed [today's date]).

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