Is CNN3 p.Ser241Leu (c.722C>T) pathogenic?

CNN3 p.Ser241Leu (c.722C>T) is classified Uncertain significance in CNN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely benign (0.2004); Ultra-rare (popmax 0.0156%, eas).

How common is CNN3 p.Ser241Leu (c.722C>T) in the general population?

CNN3 p.Ser241Leu (c.722C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CNN3 p.Ser241Leu (c.722C>T)?

AlphaMissense predicts likely benign (score 0.2004) — an in-silico prediction, not a clinical call.

CNN3 p.Ser241Leu

c.722C>T · VCV3834517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2004 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2004	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 29 kb · p 8e-12 · regional, not allelic
Overall
CADD	24.1	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 0.0156% East Asian · 7/44,896 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.000682% 11/1,613,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,414
European (non-Finnish)	0.000339%	294,997

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.Ser241Leu
Coding: c.722C>T
MANE Select: NM_001839
Type: single nucleotide variant
Location: chr1:94898010 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.78

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-ser241leu (accessed [today's date]).

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