Is ABCB5 p.Ala985Thr (c.2953G>A) pathogenic?

ABCB5 p.Ala985Thr (c.2953G>A) is classified Uncertain significance in ABCB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.2107); Ultra-rare (popmax 0.0199%, sas).

How common is ABCB5 p.Ala985Thr (c.2953G>A) in the general population?

ABCB5 p.Ala985Thr (c.2953G>A) is ultra-rare (popmax 0.0199%, sas) (gnomAD).

What do computational predictors say about ABCB5 p.Ala985Thr (c.2953G>A)?

AlphaMissense predicts likely benign (score 0.2107) — an in-silico prediction, not a clinical call.

ABCB5 p.Ala985Thr

c.2953G>A · VCV3291450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0199%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2107	likely benign
REVEL	0.744	pathogenic-leaning
SaProt	LLR -9.16	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-15 · regional, not allelic
Overall
CADD	24.5	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 0.0199% South Asian · 18/90,604 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00186% 30/1,612,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0199%	5,034
Remaining individualsnot grpmax-eligible	0.00961%	10,403
East Asian	0.00671%	14,913
European (non-Finnish)	0.000254%	393,072

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: ABCB5
Protein: p.Ala985Thr
Coding: c.2953G>A
MANE Select: NM_001163941
Type: single nucleotide variant
Location: chr7:20739068 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01

Full ABCB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB5 p.Ala350Thr Likely benign ★★ ⚠ same type
ABCB5 p.Val1209Ala Likely benign ★★ ⚠ same type
ABCB5 p.Ala1112Thr Uncertain significance ★ ⚠ same type
ABCB5 p.Ala1154Gly Uncertain significance ★ ⚠ same type
ABCB5 p.Ala221Val Uncertain significance ★ ⚠ same type
ABCB5 p.Ala223Ser Uncertain significance ★ ⚠ same type
ABCB5 p.Ala327Thr Uncertain significance ★ ⚠ same type
ABCB5 p.Ala501Glu Uncertain significance ★ ⚠ 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/abcb5-p-ala985thr (accessed [today's date]).

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