Is ABCC4 p.Phe716Tyr (c.2147T>A) pathogenic?

ABCC4 p.Phe716Tyr (c.2147T>A) is classified Uncertain significance in ABCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). AlphaMissense: likely benign (0.2305); Absent from gnomAD v4.1.

How common is ABCC4 p.Phe716Tyr (c.2147T>A) in the general population?

ABCC4 p.Phe716Tyr (c.2147T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC4 p.Phe716Tyr (c.2147T>A)?

AlphaMissense predicts likely benign (score 0.2305) — an in-silico prediction, not a clinical call.

ABCC4 p.Phe716Tyr

c.2147T>A · VCV3302236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2305 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2305	likely benign
REVEL	0.566	indeterminate
SaProt	LLR -9.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.34, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 185 kb · p 0.00034 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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.Phe716Tyr
Coding: c.2147T>A
MANE Select: NM_005845
Type: single nucleotide variant
Location: chr13:95164406 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 716: an α-helix; the abc transmembrane type-1 2 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-phe716tyr (accessed [today's date]).

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