Is ABCA5 p.Arg1439Ter (c.4315C>T) pathogenic?

ABCA5 p.Arg1439Ter (c.4315C>T) is classified Likely pathogenic in ABCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). Ultra-rare (popmax 0.0134%, afr); Associated with gingival fibromatosis-hypertrichosis syndrome.

What condition is associated with ABCA5 p.Arg1439Ter (c.4315C>T)?

ABCA5 p.Arg1439Ter (c.4315C>T) is associated with gingival fibromatosis-hypertrichosis syndrome (ClinVar).

How common is ABCA5 p.Arg1439Ter (c.4315C>T) in the general population?

ABCA5 p.Arg1439Ter (c.4315C>T) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

ABCA5 p.Arg1439Ter

c.4315C>T · rs372523620 · VCV3065938

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Conditions

gingival fibromatosis-hypertrichosis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 33 of 39
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% African / African-American · 10/74,848 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00372% 60/1,611,708 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,485
East Asian	0.0067%	14,931
Admixed American	0.00668%	14,977
Remaining individualsnot grpmax-eligible	0.00641%	15,598
European (non-Finnish)	0.00322%	31,015
South Asian	0.0011%	90,902

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: ABCA5
Protein: p.Arg1439Ter
Coding: c.4315C>T
MANE Select: NM_172232
dbSNP: rs372523620
Type: single nucleotide variant
Location: chr17:69253799 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.12
Residue 1439: the abc transporter 2 domain

Full ABCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

gingival fibromatosis-hypertrichosis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA5 p.Ser288Phe Uncertain significance ★★ ⚠ same condition
ABCA5 p.Asn190Ser Likely benign ★★ ⚠ same condition
ABCA5 p.Arg1502Ter Pathogenic ★ same condition
ABCA5 p.Glu1424Ter Likely pathogenic ★ same condition
ABCA5 c.4320+1G>C Uncertain significance ★ same condition
ABCA5 p.Pro1007Leu Uncertain significance ★ ⚠ same condition
ABCA5 p.Arg857Cys Likely pathogenic ⚠ same condition
ABCA5 p.Arg544fs Likely 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/abca5-p-arg1439ter (accessed [today's date]).

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