Is ABHD16A p.Ala412= (c.1236G>A) pathogenic?

ABHD16A p.Ala412= (c.1236G>A) is classified Benign in ABHD16A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). Low-frequency (popmax 3.48%, eas).

How common is ABHD16A p.Ala412= (c.1236G>A) in the general population?

ABHD16A p.Ala412= (c.1236G>A) is low-frequency (popmax 3.48%, eas) (gnomAD).

ABHD16A p.Ala412=

c.1236G>A · rs75509151 · VCV2571246

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.48%, 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 -13	GERP -4.1
Overall
CADD	6.153	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.48% East Asian · 1,564/44,878 alleles

Filtering AF 3.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.28%

Overall 1.08% 17,376/1,612,990 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.04%	20
East Asiangrpmax	3.48%	29
European (non-Finnish)	1.19%	84
Admixed American	0.756%	132
Remaining individualsnot grpmax-eligible	0.752%	133
Finnishnot grpmax-eligible	0.593%	169
Ashkenazi Jewishnot grpmax-eligible	0.355%	282
South Asian	0.289%	346
African / African-American	0.143%	701
Middle Eastern	0.0662%	1,512

Amish 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: ABHD16A
Protein: p.Ala412=
Coding: c.1236G>A
MANE Select: NM_021160
dbSNP: rs75509151
Type: single nucleotide variant
Location: chr6:31688737 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.90
Residue 412: a UniProt-annotated variant site (in spg86); a UniProt-annotated variant site (in spg86; no protein detected in homozygous patient cells; increased levels of phosphatidylserine and decreased levels of lysophosphatidylserine in homozygous patient cells, indicating loss of function in phosphatidylserine catabolism)

Full ABHD16A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABHD16A p.Ala412Thr Uncertain significance ★ ⚠ same residue
ABHD16A p.Ala412Val Uncertain significance ★ ⚠ same residue
ABHD16A p.Arg172Ter Pathogenic ★★ same type
ABHD16A p.Tyr87Cys Uncertain significance ★★ ⚠ same type
ABHD16A p.Val8Ile Uncertain significance ★★ ⚠ same type
ABHD16A p.Ala213= Likely benign ★★ same type
ABHD16A c.1307+1G>A Likely pathogenic ★ same type
ABHD16A p.Arg468Ter Pathogenic ★ 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/abhd16a-p-ala412 (accessed [today's date]).

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