Is ABCA12 p.Ser879= (c.2637C>T) pathogenic?

ABCA12 p.Ser879= (c.2637C>T) is classified Uncertain significance in ABCA12 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-06). Very rare (popmax 0.0011%, sas); Associated with autosomal recessive congenital ichthyosis 4A.

What condition is associated with ABCA12 p.Ser879= (c.2637C>T)?

ABCA12 p.Ser879= (c.2637C>T) is associated with autosomal recessive congenital ichthyosis 4A (ClinVar).

How common is ABCA12 p.Ser879= (c.2637C>T) in the general population?

ABCA12 p.Ser879= (c.2637C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Lamellar ichthyosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCA12 p.Ser879=

c.2637C>T · rs760070967 · VCV1047921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

autosomal recessive congenital ichthyosis 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.32	acceptor loss · deltas
Pangolin	Δ0.30	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.4	GERP -4.5
Overall
CADD	4.626	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000558% 9/1,613,664 alleles · very rare exomes 7/1,461,558 · genomes 2/152,106 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,470
South Asiangrpmax	0.0011%	91,068
European (non-Finnish)	0.000593%	168,562

Remaining individuals 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: ABCA12
Protein: p.Ser879=
Coding: c.2637C>T
MANE Select: NM_173076
dbSNP: rs760070967
Type: single nucleotide variant
Location: chr2:215004255 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 879: a UniProt-annotated variant site (in arci4b)

Full ABCA12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive congenital ichthyosis 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lamellar ichthyosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ABCA12 c.985+1G>A Likely pathogenic ★★ same condition
ABCA12 p.Arg1514Cys Pathogenic ★★ same condition
ABCA12 p.Arg1514His Pathogenic/Likely pathogenic ★★ same condition
ABCA12 p.Arg1515Ter Pathogenic ★★ same condition
ABCA12 p.Arg1950Ter Pathogenic ★★ same condition
ABCA12 p.Arg1960Ter Likely pathogenic ★★ same condition
ABCA12 p.Arg2204Ter Pathogenic ★★ same condition
ABCA12 p.Arg287Ter Pathogenic ★★ 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/abca12-p-ser879 (accessed [today's date]).

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