Is ABCA5 p.Arg857Cys (c.2569C>T) pathogenic?

ABCA5 p.Arg857Cys (c.2569C>T) is classified Likely pathogenic in ABCA5 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.3099); Ultra-rare (popmax 0.0465%, sas); Associated with gingival fibromatosis-hypertrichosis syndrome.

What condition is associated with ABCA5 p.Arg857Cys (c.2569C>T)?

ABCA5 p.Arg857Cys (c.2569C>T) is associated with gingival fibromatosis-hypertrichosis syndrome (ClinVar).

How common is ABCA5 p.Arg857Cys (c.2569C>T) in the general population?

ABCA5 p.Arg857Cys (c.2569C>T) is ultra-rare (popmax 0.0465%, sas) (gnomAD).

What do computational predictors say about ABCA5 p.Arg857Cys (c.2569C>T)?

AlphaMissense predicts likely benign (score 0.3099) — an in-silico prediction, not a clinical call.

ABCA5 p.Arg857Cys

c.2569C>T · rs747667004 · VCV2445995

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3099 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0465%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gingival fibromatosis-hypertrichosis syndrome

Computational evidence

Protein change
AlphaMissense	0.3099	likely benign ⚠ discordant with ClinVar
REVEL	0.735	pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.21	donor loss, 25 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.22 · regional, not allelic
Overall
CADD	27.8	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 0.0465% South Asian · 42/90,238 alleles

Filtering AF 0.0354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00987% 159/1,610,394 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0465%	2,149
East Asian	0.0202%	4,961
European (non-Finnish)	0.0084%	11,908
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,762
Remaining individualsnot grpmax-eligible	0.00642%	15,584
African / African-American	0.00401%	24,920

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.Arg857Cys
Coding: c.2569C>T
MANE Select: NM_172232
dbSNP: rs747667004
Type: single nucleotide variant
Location: chr17:69277666 (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.Ser288Phe Uncertain significance ★★ ⚠ same condition
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.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-arg857cys (accessed [today's date]).

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