Is ASF1A p.Ala182Val (c.545C>T) pathogenic?

ASF1A p.Ala182Val (c.545C>T) is classified Uncertain significance in ASF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0775); Ultra-rare (popmax 0.0335%, eas).

How common is ASF1A p.Ala182Val (c.545C>T) in the general population?

ASF1A p.Ala182Val (c.545C>T) is ultra-rare (popmax 0.0335%, eas) (gnomAD).

What do computational predictors say about ASF1A p.Ala182Val (c.545C>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

ASF1A p.Ala182Val

c.545C>T · VCV3435882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -6.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 115 bp · p 0.66 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0335% East Asian · 15/44,832 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00112% 18/1,613,566 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0335%	2,989
European (non-Finnish)	0.000254%	393,236

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: ASF1A
Protein: p.Ala182Val
Coding: c.545C>T
MANE Select: NM_014034
Type: single nucleotide variant
Location: chr6:118907544 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 24 PDB
Residue 182: the 'required for interaction with hira' region

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

Similar variants

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
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-ala182val (accessed [today's date]).

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