Is ABCC4 p.Val900Leu (c.2698G>T) pathogenic?

ABCC4 p.Val900Leu (c.2698G>T) is classified Likely benign in ABCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-27). AlphaMissense: likely pathogenic (0.667); Low-frequency (popmax 1.1%, amr).

How common is ABCC4 p.Val900Leu (c.2698G>T) in the general population?

ABCC4 p.Val900Leu (c.2698G>T) is low-frequency (popmax 1.1%, amr) (gnomAD).

What do computational predictors say about ABCC4 p.Val900Leu (c.2698G>T)?

AlphaMissense predicts likely pathogenic (score 0.667) — an in-silico prediction, not a clinical call.

ABCC4 p.Val900Leu

c.2698G>T · VCV4683812

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.667 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.667	likely pathogenic
REVEL	0.677	pathogenic-leaning
SaProt	LLR -10.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 185 kb · p 0.00034 · regional, not allelic
Overall
CADD	26.1	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 1.1% Admixed American · 659/60,018 alleles

Filtering AF 1.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 1%

Overall 0.0448% 723/1,614,108 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	1.1%	91
Remaining individualsnot grpmax-eligible	0.0896%	1,116
African / African-American	0.008%	12,507
European (non-Finnish)	0.000169%	589,991

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: ABCC4
Protein: p.Val900Leu
Coding: c.2698G>T
MANE Select: NM_005845
Type: single nucleotide variant
Location: chr13:95075540 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 900: a UniProt-annotated variant site (in); 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-val900leu (accessed [today's date]).

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