Is CNN2 p.Met201Val (c.601A>G) pathogenic?

CNN2 p.Met201Val (c.601A>G) is classified Uncertain significance in CNN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.0891); Ultra-rare (popmax 0.0254%, afr).

How common is CNN2 p.Met201Val (c.601A>G) in the general population?

CNN2 p.Met201Val (c.601A>G) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about CNN2 p.Met201Val (c.601A>G)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

CNN2 p.Met201Val

c.601A>G · VCV4004300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -5.14	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 6.8	GERP -1.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 11 kb · p 0.17 · regional, not allelic
Overall
CADD	21.1	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 0.0254% African / African-American · 19/74,876 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00205% 33/1,613,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,941
Remaining individualsnot grpmax-eligible	0.00801%	12,491
Admixed American	0.00333%	29,985
South Asian	0.0011%	91,070
European (non-Finnish)	0.000509%	196,554

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: CNN2
Protein: p.Met201Val
Coding: c.601A>G
MANE Select: NM_004368
Type: single nucleotide variant
Location: chr19:1036509 (GRCh38)
Gene constraint: LOEUF 1.006 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.62 · 1 PDB

Full CNN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNN2 p.Met201Thr Uncertain significance ★ ⚠ same residue
CNN2 p.Ala126Ser Uncertain significance ★ ⚠ same type
CNN2 p.Ala126Thr Uncertain significance ★ ⚠ same type
CNN2 p.Ala161Thr Uncertain significance ★ ⚠ same type
CNN2 p.Arg227Trp Uncertain significance ★ ⚠ same type
CNN2 p.Arg266Gly Uncertain significance ★ ⚠ same type
CNN2 p.Arg35Cys Uncertain significance ★ ⚠ same type
CNN2 p.Arg35His 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/cnn2-p-met201val (accessed [today's date]).

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