Is CSRNP2 p.Ile263Phe (c.787A>T) pathogenic?

CSRNP2 p.Ile263Phe (c.787A>T) is classified Uncertain significance in CSRNP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely pathogenic (0.8213); Very rare (popmax 0.00112%, sas).

How common is CSRNP2 p.Ile263Phe (c.787A>T) in the general population?

CSRNP2 p.Ile263Phe (c.787A>T) is very rare (popmax 0.00112%, sas) (gnomAD).

What do computational predictors say about CSRNP2 p.Ile263Phe (c.787A>T)?

AlphaMissense predicts likely pathogenic (score 0.8213) — an in-silico prediction, not a clinical call.

CSRNP2 p.Ile263Phe

c.787A>T · VCV3497922

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8213	likely pathogenic
REVEL	0.129	moderately benign-leaning
SaProt	LLR -12.17	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 12 kb · p 3.3e-17 · regional, not allelic
Overall
CADD	27.4	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 0.00112% South Asian · 1/89,088 alleles

Overall 6.93e-05% 1/1,442,890 alleles · very rare

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: CSRNP2
Protein: p.Ile263Phe
Coding: c.787A>T
MANE Select: NM_030809
Type: single nucleotide variant
Location: chr12:51064591 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.02

Full CSRNP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSRNP2 p.Ile263Val Uncertain significance ★ ⚠ same residue
CSRNP2 p.Ala255Val Uncertain significance ★ ⚠ same type
CSRNP2 p.Ala289Thr Uncertain significance ★ ⚠ same type
CSRNP2 p.Arg123Cys Uncertain significance ★ ⚠ same type
CSRNP2 p.Arg184Gln Uncertain significance ★ ⚠ same type
CSRNP2 p.Arg194His Uncertain significance ★ ⚠ same type
CSRNP2 p.Arg218Gln Uncertain significance ★ ⚠ same type
CSRNP2 p.Arg282Gln 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/csrnp2-p-ile263phe (accessed [today's date]).

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