Is CNN1 p.Asp104Val (c.311A>T) pathogenic?

CNN1 p.Asp104Val (c.311A>T) is classified Uncertain significance in CNN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-09). AlphaMissense: likely pathogenic (0.9799); Absent from gnomAD v4.1.

How common is CNN1 p.Asp104Val (c.311A>T) in the general population?

CNN1 p.Asp104Val (c.311A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNN1 p.Asp104Val (c.311A>T)?

AlphaMissense predicts likely pathogenic (score 0.9799) — an in-silico prediction, not a clinical call.

CNN1 p.Asp104Val

c.311A>T · rs2512688229 · VCV2287961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9799	likely pathogenic
REVEL	0.641	indeterminate
SaProt	LLR -12.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.88, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 11 kb · p 1.5e-05 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNN1
Protein: p.Asp104Val
Coding: c.311A>T
MANE Select: NM_001299
dbSNP: rs2512688229
Type: single nucleotide variant
Location: chr19:11546890 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.06 · 1 PDB
Residue 104: the calponin-homology (ch) domain; an α-helix

Full CNN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNN1 p.Asp104Asn Uncertain significance ★ ⚠ same residue
CNN1 p.Val243Ile Uncertain significance ★★ ⚠ same type
CNN1 p.Ala145Thr Uncertain significance ★ ⚠ same type
CNN1 p.Ala290Val Uncertain significance ★ ⚠ same type
CNN1 p.Ala297Thr Uncertain significance ★ ⚠ same type
CNN1 p.Arg150Gln Uncertain significance ★ ⚠ same type
CNN1 p.Arg158Lys Uncertain significance ★ ⚠ same type
CNN1 p.Arg185Gln 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/cnn1-p-asp104val (accessed [today's date]).

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