Is CARNMT1 p.Asp307Asn (c.919G>A) pathogenic?

CARNMT1 p.Asp307Asn (c.919G>A) is classified Uncertain significance in CARNMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: ambiguous (0.4755); Very rare (popmax 0.00588%, amr).

How common is CARNMT1 p.Asp307Asn (c.919G>A) in the general population?

CARNMT1 p.Asp307Asn (c.919G>A) is very rare (popmax 0.00588%, amr) (gnomAD).

What do computational predictors say about CARNMT1 p.Asp307Asn (c.919G>A)?

AlphaMissense predicts ambiguous (score 0.4755) — an in-silico prediction, not a clinical call.

CARNMT1 p.Asp307Asn

c.919G>A · VCV4219188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4755 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, amr)

Computational evidence

Protein change
AlphaMissense	0.4755	ambiguous
REVEL	0.292	indeterminate
SaProt	LLR -9.78	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 34 kb · p 3.4e-09 · regional, not allelic
Overall
CADD	26.8	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 0.00588% Admixed American · 3/51,010 alleles

Filtering AF 0.00156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000832%

Overall 0.000448% 7/1,562,450 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00588%	17,003
Remaining individualsnot grpmax-eligible	0.0033%	30,325
European (non-Finnish)	0.000174%	575,556

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: CARNMT1
Protein: p.Asp307Asn
Coding: c.919G>A
MANE Select: NM_152420
Type: single nucleotide variant
Location: chr9:74996552 (GRCh38)
Gene constraint: LOEUF 1.157 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.52 · 3 PDB
Residue 307: a β-strand

Full CARNMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CARNMT1 p.Asp295= Benign ★★ same type
CARNMT1 p.Ala49Val Uncertain significance ★ ⚠ same type
CARNMT1 p.Arg13Pro Uncertain significance ★ ⚠ same type
CARNMT1 p.Arg63His Uncertain significance ★ ⚠ same type
CARNMT1 p.Arg83Gln Uncertain significance ★ ⚠ same type
CARNMT1 p.Asn249His Uncertain significance ★ ⚠ same type
CARNMT1 p.Asn288Asp Uncertain significance ★ ⚠ same type
CARNMT1 p.Asn353Ser 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/carnmt1-p-asp307asn (accessed [today's date]).

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