Is DBN1 p.Ala244Val (c.731C>T) pathogenic?

DBN1 p.Ala244Val (c.731C>T) is classified Uncertain significance in DBN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: ambiguous (0.3442); Very rare (popmax 0.00667%, afr).

How common is DBN1 p.Ala244Val (c.731C>T) in the general population?

DBN1 p.Ala244Val (c.731C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about DBN1 p.Ala244Val (c.731C>T)?

AlphaMissense predicts ambiguous (score 0.3442) — an in-silico prediction, not a clinical call.

DBN1 p.Ala244Val

c.731C>T · rs376817792 · VCV2599851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3442 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3442	ambiguous
REVEL	0.151	moderately benign-leaning
SaProt	LLR -7.58	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.84 · regional, not allelic
Overall
CADD	26.6	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 0.00667% African / African-American · 5/74,908 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000682% 11/1,614,002 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,982
South Asian	0.0011%	91,082
European (non-Finnish)	0.000424%	236,004

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: DBN1
Protein: p.Ala244Val
Coding: c.731C>T
MANE Select: NM_001363541
dbSNP: rs376817792
Type: single nucleotide variant
Location: chr5:177466812 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.93 · 5 PDB
Residue 244: the 'disordered' region

Full DBN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBN1 c.86+1283G>A Uncertain significance ★ same type
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DBN1 c.86+1299A>T Uncertain significance ★ same type
DBN1 p.Ala126Val Uncertain significance ★ ⚠ same type
DBN1 p.Ala27Thr Uncertain significance ★ ⚠ same type
DBN1 p.Ala455Val Uncertain significance ★ ⚠ same type
DBN1 p.Ala485Thr Uncertain significance ★ ⚠ same type
DBN1 p.Ala532Thr 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/dbn1-p-ala244val (accessed [today's date]).

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