Is DBF4B p.Tyr545His (c.1633T>C) pathogenic?

DBF4B p.Tyr545His (c.1633T>C) is classified Likely benign in DBF4B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-31). AlphaMissense: ambiguous (0.3403); Ultra-rare (popmax 0.012%, afr).

How common is DBF4B p.Tyr545His (c.1633T>C) in the general population?

DBF4B p.Tyr545His (c.1633T>C) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about DBF4B p.Tyr545His (c.1633T>C)?

AlphaMissense predicts ambiguous (score 0.3403) — an in-silico prediction, not a clinical call.

DBF4B p.Tyr545His

c.1633T>C · rs150145616 · VCV2407417

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3403 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3403	ambiguous
REVEL	0.071	moderately benign-leaning
SaProt	LLR -4.99	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 -1.1	GERP -2.4
Regional constraint	o/e 0.90	unconstrained · MANE · 21 kb · p 0.0076 · regional, not allelic
Overall
CADD	4.587	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 0.012% African / African-American · 9/74,928 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.000682% 11/1,614,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,325
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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: DBF4B
Protein: p.Tyr545His
Coding: c.1633T>C
MANE Select: NM_145663
dbSNP: rs150145616
Type: single nucleotide variant
Location: chr17:44751038 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.60

Full DBF4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBF4B p.Val89Met Uncertain significance ★★ ⚠ same type
DBF4B p.Ala197Val Uncertain significance ★ ⚠ same type
DBF4B p.Ala331Val Uncertain significance ★ ⚠ same type
DBF4B p.Ala361Thr Uncertain significance ★ ⚠ same type
DBF4B p.Ala383Thr Uncertain significance ★ ⚠ same type
DBF4B p.Ala499Ser Uncertain significance ★ ⚠ same type
DBF4B p.Ala69Thr Uncertain significance ★ ⚠ same type
DBF4B p.Arg131Ser 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/dbf4b-p-tyr545his (accessed [today's date]).

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