Is ASF1B p.Arg145Trp (c.433C>T) pathogenic?

ASF1B p.Arg145Trp (c.433C>T) is classified Uncertain significance in ASF1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely pathogenic (0.9879); Very rare (popmax 0.00334%, amr).

How common is ASF1B p.Arg145Trp (c.433C>T) in the general population?

ASF1B p.Arg145Trp (c.433C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ASF1B p.Arg145Trp (c.433C>T)?

AlphaMissense predicts likely pathogenic (score 0.9879) — an in-silico prediction, not a clinical call.

ASF1B p.Arg145Trp

c.433C>T · rs755215195 · VCV2514332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9879	likely pathogenic
REVEL	0.6	indeterminate
SaProt	LLR -17.42	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 5.1	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 16 kb · p 0.11 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.00334% Admixed American · 2/59,962 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.0026% 42/1,613,842 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,981
European (non-Finnish)	0.00305%	32,778
African / African-American	0.00267%	37,425
South Asian	0.0022%	45,536

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: ASF1B
Protein: p.Arg145Trp
Coding: c.433C>T
MANE Select: NM_018154
dbSNP: rs755215195
Type: single nucleotide variant
Location: chr19:14120635 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 85.71 · 4 PDB
Residue 145: the 'interaction with histone h3' region; the 'interaction with chaf1b' region; a β-strand

Full ASF1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASF1B p.Arg145Leu Uncertain significance ★ ⚠ same residue
ASF1B p.Ala76Thr Uncertain significance ★ ⚠ same type
ASF1B p.Arg123Cys Uncertain significance ★ ⚠ same type
ASF1B p.Arg123His Uncertain significance ★ ⚠ same type
ASF1B p.Arg137Gln Uncertain significance ★ ⚠ same type
ASF1B p.Arg23Leu Uncertain significance ★ ⚠ same type
ASF1B p.Asp154Asn Uncertain significance ★ ⚠ same type
ASF1B p.Asp154Gly 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/asf1b-p-arg145trp (accessed [today's date]).

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