Is CSRNP2 p.Val358Met (c.1072G>A) pathogenic?

CSRNP2 p.Val358Met (c.1072G>A) is classified Uncertain significance in CSRNP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: ambiguous (0.3433); Ultra-rare (popmax 0.0335%, nfe).

How common is CSRNP2 p.Val358Met (c.1072G>A) in the general population?

CSRNP2 p.Val358Met (c.1072G>A) is ultra-rare (popmax 0.0335%, nfe) (gnomAD).

What do computational predictors say about CSRNP2 p.Val358Met (c.1072G>A)?

AlphaMissense predicts ambiguous (score 0.3433) — an in-silico prediction, not a clinical call.

CSRNP2 p.Val358Met

c.1072G>A · rs138451611 · VCV2367550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3433 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3433	ambiguous
REVEL	0.098	moderately benign-leaning
SaProt	LLR -7.86	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.55	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 794 bp · p 0.0097 · regional, not allelic
Overall
CADD	23.8	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 0.0335% European (non-Finnish) · 395/1,179,928 alleles

Filtering AF 0.0307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.0255% 412/1,613,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0335%	2,987
Remaining individualsnot grpmax-eligible	0.016%	6,247
African / African-American	0.00801%	12,491
Finnishnot grpmax-eligible	0.00156%	64,012

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.Val358Met
Coding: c.1072G>A
MANE Select: NM_030809
dbSNP: rs138451611
Type: single nucleotide variant
Location: chr12:51064306 (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.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
CSRNP2 p.Arg286Leu 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-val358met (accessed [today's date]).

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