Is ABCA5 p.Ser278Pro (c.832T>C) pathogenic?

ABCA5 p.Ser278Pro (c.832T>C) is classified Uncertain significance in ABCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely pathogenic (0.9804); Absent from gnomAD v4.1.

How common is ABCA5 p.Ser278Pro (c.832T>C) in the general population?

ABCA5 p.Ser278Pro (c.832T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA5 p.Ser278Pro (c.832T>C)?

AlphaMissense predicts likely pathogenic (score 0.9804) — an in-silico prediction, not a clinical call.

ABCA5 p.Ser278Pro

c.832T>C · rs2509599882 · VCV2257313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9804 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,164)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9804	likely pathogenic · top 4% in ABCA5
REVEL	0.892	moderately pathogenic-leaning
SaProt	LLR -15.04	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.25	acceptor loss, 16 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 0.53, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.22 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,608,164). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCA5
Protein: p.Ser278Pro
Coding: c.832T>C
MANE Select: NM_172232
dbSNP: rs2509599882
Type: single nucleotide variant
Location: chr17:69304767 (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

Similar variants

ABCA5 p.Ser288Phe Uncertain significance ★★ ⚠ same type
ABCA5 c.4765+3A>G Likely benign ★★ same type
ABCA5 p.Asn190Ser Likely benign ★★ ⚠ same type
ABCA5 p.Asn768Asp Benign ★★ same type
ABCA5 p.Asp817Tyr Likely benign ★★ ⚠ same type
ABCA5 p.Gly1159Arg Likely benign ★★ ⚠ same type
ABCA5 p.Gly128= Benign/Likely benign ★★ same type
ABCA5 p.Ile1173Val Likely benign ★★ 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/abca5-p-ser278pro (accessed [today's date]).

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