Is ASF1A p.Ala67Ser (c.199G>T) pathogenic?

ASF1A p.Ala67Ser (c.199G>T) is classified Uncertain significance in ASF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: ambiguous (0.3716); Absent from gnomAD v4.1.

How common is ASF1A p.Ala67Ser (c.199G>T) in the general population?

ASF1A p.Ala67Ser (c.199G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASF1A p.Ala67Ser (c.199G>T)?

AlphaMissense predicts ambiguous (score 0.3716) — an in-silico prediction, not a clinical call.

ASF1A p.Ala67Ser

c.199G>T · VCV4643450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3716 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3716	ambiguous
REVEL	0.278	benign-leaning
SaProt	LLR -8.08	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 2, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 13 kb · p 7e-13 · regional, not allelic
Overall
CADD	24.2	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

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.Ala67Ser
Coding: c.199G>T
MANE Select: NM_014034
Type: single nucleotide variant
Location: chr6:118900855 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 24 PDB
Residue 67: the 'interaction with histone h3, chaf1b, and hira' region; a β-strand

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.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
ASF1A p.Leu122Phe 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-ala67ser (accessed [today's date]).

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