Is ACSS2 p.His252= (c.756C>T) pathogenic?

ACSS2 p.His252= (c.756C>T) is classified Benign in ACSS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-16). Rare (popmax 0.165%, nfe); Associated with ACSS2-related disorder.

What condition is associated with ACSS2 p.His252= (c.756C>T)?

ACSS2 p.His252= (c.756C>T) is associated with ACSS2-related disorder (ClinVar).

How common is ACSS2 p.His252= (c.756C>T) in the general population?

ACSS2 p.His252= (c.756C>T) is rare (popmax 0.165%, nfe) (gnomAD).

ACSS2 p.His252=

c.756C>T · rs61014667 · VCV3043533

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.165%, nfe)

Conditions

ACSS2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP 1.5, phastCons 1
Overall
CADD	6.822	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% European (non-Finnish) · 1,949/1,179,904 alleles

Filtering AF 0.159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.157%

Overall 0.206% 3,331/1,613,900 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.63%	62
Remaining individualsnot grpmax-eligible	0.189%	530
European (non-Finnish)grpmax	0.165%	605
Admixed American	0.163%	612
South Asian	0.119%	843
Middle Eastern	0.0495%	2,019
African / African-American	0.0187%	5,360

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACSS2
Protein: p.His252=
Coding: c.756C>T
MANE Select: NM_018677
dbSNP: rs61014667
Type: single nucleotide variant
Location: chr20:34914359 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.14

Full ACSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACSS2-related disorder

Similar variants

ACSS2 p.Arg153Gln Uncertain significance ⚠ same condition
ACSS2 p.Arg696His Uncertain significance same condition
ACSS2 p.Ala307= Likely benign same condition
ACSS2 p.Asp309= Likely benign same condition
ACSS2 p.Lys342= Likely benign same condition
ACSS2 p.Pro486= Likely benign same condition
ACSS2 p.Thr137= Likely benign same condition
ACSS2 p.Thr628= Likely benign same condition

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/acss2-p-his252 (accessed [today's date]).

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