Is CNN3 p.Asn114Ser (c.341A>G) pathogenic?

CNN3 p.Asn114Ser (c.341A>G) is classified Uncertain significance in CNN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.8384); Very rare (popmax 0.000593%, nfe).

How common is CNN3 p.Asn114Ser (c.341A>G) in the general population?

CNN3 p.Asn114Ser (c.341A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CNN3 p.Asn114Ser (c.341A>G)?

AlphaMissense predicts likely pathogenic (score 0.8384) — an in-silico prediction, not a clinical call.

CNN3 p.Asn114Ser

c.341A>G · VCV4830363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8384 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8384	likely pathogenic
REVEL	0.41	indeterminate
SaProt	LLR -9.81	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 29 kb · p 8e-12 · regional, not allelic
Overall
CADD	25.8	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 0.000593% European (non-Finnish) · 7/1,179,610 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,604 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.Asn114Ser
Coding: c.341A>G
MANE Select: NM_001839
Type: single nucleotide variant
Location: chr1:94902164 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.78
Residue 114: 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.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
CNN3 p.Glu311Lys 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-asn114ser (accessed [today's date]).

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