Is ABCB5 p.Tyr122Phe (c.365A>T) pathogenic?

ABCB5 p.Tyr122Phe (c.365A>T) is classified Uncertain significance in ABCB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.1173); Ultra-rare (popmax 0.0495%, mid).

How common is ABCB5 p.Tyr122Phe (c.365A>T) in the general population?

ABCB5 p.Tyr122Phe (c.365A>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about ABCB5 p.Tyr122Phe (c.365A>T)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

ABCB5 p.Tyr122Phe

c.365A>T · rs202100779 · VCV2395412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.644	pathogenic-leaning
SaProt	LLR -7.57	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.48	acceptor gain · deltas
Pangolin	Δ0.46	gain · loss 0.22 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 0.62, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-15 · regional, not allelic
Overall
CADD	24.2	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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.017%

Overall 0.0156% 251/1,613,556 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
European (non-Finnish)	0.0199%	5,020
Remaining individualsnot grpmax-eligible	0.0112%	8,925
Admixed American	0.00835%	11,981
African / African-American	0.00133%	75,070

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.Tyr122Phe
Coding: c.365A>T
MANE Select: NM_001163941
dbSNP: rs202100779
Type: single nucleotide variant
Location: chr7:20643234 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01
Residue 122: the abc transmembrane type-1 1 domain

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-tyr122phe (accessed [today's date]).

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