Is ABCC4 p.Phe620Leu (c.1858T>C) pathogenic?

ABCC4 p.Phe620Leu (c.1858T>C) is classified Uncertain significance in ABCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-23). AlphaMissense: likely pathogenic (0.638); Absent from gnomAD v4.1.

How common is ABCC4 p.Phe620Leu (c.1858T>C) in the general population?

ABCC4 p.Phe620Leu (c.1858T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC4 p.Phe620Leu (c.1858T>C)?

AlphaMissense predicts likely pathogenic (score 0.638) — an in-silico prediction, not a clinical call.

ABCC4 p.Phe620Leu

c.1858T>C · rs2502182794 · VCV2262194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.638 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.638	likely pathogenic
REVEL	0.231	benign-leaning
SaProt	LLR -0.18	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 185 kb · p 0.00034 · regional, not allelic
Overall
CADD	19.41	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC4
Protein: p.Phe620Leu
Coding: c.1858T>C
MANE Select: NM_005845
dbSNP: rs2502182794
Type: single nucleotide variant
Location: chr13:95166334 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 620: the abc transporter 1 domain

Full ABCC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC4 p.Ala1282Thr Uncertain significance ★★ ⚠ same type
ABCC4 p.Ala1324Thr Uncertain significance ★★ ⚠ same type
ABCC4 p.Leu238Phe Uncertain significance ★★ ⚠ same type
ABCC4 p.Tyr788Cys Uncertain significance ★★ ⚠ same type
ABCC4 c.1825-7A>G Benign ★★ same type
ABCC4 c.185+7C>T Benign ★★ same type
ABCC4 c.307-10C>T Benign/Likely benign ★★ same type
ABCC4 p.Ala700= 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/abcc4-p-phe620leu (accessed [today's date]).

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