Is ASF1A p.Pro144Ser (c.430C>T) pathogenic?

ASF1A p.Pro144Ser (c.430C>T) is classified Uncertain significance in ASF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1.

How common is ASF1A p.Pro144Ser (c.430C>T) in the general population?

ASF1A p.Pro144Ser (c.430C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASF1A p.Pro144Ser (c.430C>T)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

ASF1A p.Pro144Ser

c.430C>T · VCV3317927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -11.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.46	acceptor gain, 5 bp away · masked 0 · deltas
Pangolin	Δ0.23	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 13 kb · p 7e-13 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASF1A
Protein: p.Pro144Ser
Coding: c.430C>T
MANE Select: NM_014034
Type: single nucleotide variant
Location: chr6:118907429 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 24 PDB
Residue 144: the 'interaction with histone h3, chaf1b, and hira' region

Full ASF1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASF1A p.Ala182Val Uncertain significance ★ ⚠ same type
ASF1A p.Ala67Ser Uncertain significance ★ ⚠ same type
ASF1A p.Asn8Ser Uncertain significance ★ ⚠ same type
ASF1A p.Asp162Gly Uncertain significance ★ ⚠ same type
ASF1A p.Gln171Arg Uncertain significance ★ ⚠ same type
ASF1A p.Glu29Asp Uncertain significance ★ ⚠ same type
ASF1A p.Gly185Glu Uncertain significance ★ ⚠ same type
ASF1A p.His200Pro 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/asf1a-p-pro144ser (accessed [today's date]).

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