Is CNN3 p.Met98Val (c.292A>G) pathogenic?

CNN3 p.Met98Val (c.292A>G) is classified Uncertain significance in CNN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-27). AlphaMissense: likely benign (0.16); Very rare (popmax 8.48e-05%, nfe).

How common is CNN3 p.Met98Val (c.292A>G) in the general population?

CNN3 p.Met98Val (c.292A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CNN3 p.Met98Val (c.292A>G)?

AlphaMissense predicts likely benign (score 0.16) — an in-silico prediction, not a clinical call.

CNN3 p.Met98Val

c.292A>G · rs1670887771 · VCV2606651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.16 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.16	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -6.23	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 5.1	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 29 kb · p 8e-12 · regional, not allelic
Overall
CADD	22.2	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 8.48e-05% European (non-Finnish) · 1/1,178,746 alleles

Overall 6.85e-05% 1/1,460,428 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: CNN3
Protein: p.Met98Val
Coding: c.292A>G
MANE Select: NM_001839
dbSNP: rs1670887771
Type: single nucleotide variant
Location: chr1:94902213 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.78
Residue 98: the calponin-homology (ch) domain

Full CNN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNN3 p.Ala217Thr Uncertain significance ★ ⚠ same type
CNN3 p.Asn114Ser Uncertain significance ★ ⚠ same type
CNN3 p.Asn34Ser Uncertain significance ★ ⚠ same type
CNN3 p.Asp196Gly Uncertain significance ★ ⚠ same type
CNN3 p.Asp230Asn Uncertain significance ★ ⚠ same type
CNN3 p.Asp324Asn Uncertain significance ★ ⚠ same type
CNN3 p.Glu146Asp Uncertain significance ★ ⚠ same type
CNN3 p.Glu294Asp 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/cnn3-p-met98val (accessed [today's date]).

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