Is ABCA5 p.Ser288Phe (c.863C>T) pathogenic?

ABCA5 p.Ser288Phe (c.863C>T) is classified Uncertain significance in ABCA5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-20). AlphaMissense: ambiguous (0.4426); Ultra-rare (popmax 0.0135%, amr); Associated with gingival fibromatosis-hypertrichosis syndrome.

What condition is associated with ABCA5 p.Ser288Phe (c.863C>T)?

ABCA5 p.Ser288Phe (c.863C>T) is associated with gingival fibromatosis-hypertrichosis syndrome (ClinVar).

How common is ABCA5 p.Ser288Phe (c.863C>T) in the general population?

ABCA5 p.Ser288Phe (c.863C>T) is ultra-rare (popmax 0.0135%, amr) (gnomAD).

What do computational predictors say about ABCA5 p.Ser288Phe (c.863C>T)?

AlphaMissense predicts ambiguous (score 0.4426) — an in-silico prediction, not a clinical call.

ABCA5 p.Ser288Phe

c.863C>T · VCV3517167

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4426 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

gingival fibromatosis-hypertrichosis syndrome

Computational evidence

Protein change
AlphaMissense	0.4426	ambiguous
REVEL	0.227	benign-leaning
SaProt	LLR -6.46	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.22 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% Admixed American · 8/59,468 alleles

Filtering AF 0.00667% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00486%

Overall 0.00193% 31/1,609,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0135%	7,434
South Asian	0.00885%	11,300
European (non-Finnish)	0.00127%	78,518

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.Ser288Phe
Coding: c.863C>T
MANE Select: NM_172232
Type: single nucleotide variant
Location: chr17:69304736 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.12

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.Asn190Ser Likely benign ★★ ⚠ same condition
ABCA5 p.Arg1439Ter Likely pathogenic ★ 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-ser288phe (accessed [today's date]).

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