Is ACACA p.Ala812= (c.2436C>T) pathogenic?

ACACA p.Ala812= (c.2436C>T) is classified Likely benign in ACACA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). Ultra-rare (popmax 0.0178%, eas).

How common is ACACA p.Ala812= (c.2436C>T) in the general population?

ACACA p.Ala812= (c.2436C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

ACACA p.Ala812=

c.2436C>T · rs148504028 · VCV1613141

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

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 0.97	GERP -1.5, phastCons 0.98
Overall
CADD	13.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,884 alleles

Filtering AF 0.0107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.01%

Overall 0.0123% 198/1,613,908 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
Finnishnot grpmax-eligible	0.0313%	3,194
East Asiangrpmax	0.0178%	5,611
European (non-Finnish)	0.0124%	8,082
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.005%	19,999
African / African-American	0.004%	24,994
South Asian	0.0011%	91,058

Ashkenazi Jewish 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: ACACA
Protein: p.Ala812=
Coding: c.2436C>T
MANE Select: NM_198834
dbSNP: rs148504028
Type: single nucleotide variant
Location: chr17:37246850 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 10 PDB
Residue 812: the biotinyl-binding domain

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

Similar variants

ACACA p.Ala812Val Uncertain significance ★ ⚠ same residue
ACACA p.Ala2308Val Uncertain significance ★★ ⚠ same type
ACACA p.Arg1206His Uncertain significance ★★ ⚠ same type
ACACA p.Arg2198Gln Uncertain significance ★★ ⚠ same type
ACACA p.Arg745Trp Uncertain significance ★★ ⚠ same type
ACACA p.Asn1903Ser Uncertain significance ★★ ⚠ same type
ACACA p.Asn728Ser Uncertain significance ★★ ⚠ same type
ACACA p.Asn950Ser 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/acaca-p-ala812 (accessed [today's date]).

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