Is ASF1B p.Val6Met (c.16G>A) pathogenic?

ASF1B p.Val6Met (c.16G>A) is classified Uncertain significance in ASF1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely pathogenic (0.9555); Ultra-rare (popmax 0.0214%, afr).

How common is ASF1B p.Val6Met (c.16G>A) in the general population?

ASF1B p.Val6Met (c.16G>A) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about ASF1B p.Val6Met (c.16G>A)?

AlphaMissense predicts likely pathogenic (score 0.9555) — an in-silico prediction, not a clinical call.

ASF1B p.Val6Met

c.16G>A · VCV3952155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9555 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9555	likely pathogenic
REVEL	0.557	indeterminate
SaProt	LLR -11.42	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 7.4	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 16 kb · p 0.11 · regional, not allelic
Overall
CADD	27.6	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 0.0214% African / African-American · 16/74,914 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00105% 17/1,613,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,682
Admixed American	0.00167%	59,966

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.Val6Met
Coding: c.16G>A
MANE Select: NM_018154
Type: single nucleotide variant
Location: chr19:14136441 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 85.71 · 4 PDB
Residue 6: the 'interaction with histone h3' region; a β-strand; the 'interaction with chaf1b' region

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

Similar variants

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.Arg145Leu Uncertain significance ★ ⚠ same type
ASF1B p.Arg145Trp Uncertain significance ★ ⚠ same type
ASF1B p.Arg23Leu Uncertain significance ★ ⚠ same type
ASF1B p.Asp154Asn 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-val6met (accessed [today's date]).

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