Is ABCC4 p.Pro403Leu (c.1208C>T) pathogenic?

ABCC4 p.Pro403Leu (c.1208C>T) is classified Likely benign in ABCC4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-22). AlphaMissense: likely benign (0.0703); Rare (popmax 0.405%, afr); Associated with ABCC4-related disorder.

What condition is associated with ABCC4 p.Pro403Leu (c.1208C>T)?

ABCC4 p.Pro403Leu (c.1208C>T) is associated with ABCC4-related disorder (ClinVar).

How common is ABCC4 p.Pro403Leu (c.1208C>T) in the general population?

ABCC4 p.Pro403Leu (c.1208C>T) is rare (popmax 0.405%, afr) (gnomAD).

What do computational predictors say about ABCC4 p.Pro403Leu (c.1208C>T)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

ABCC4 p.Pro403Leu

c.1208C>T · rs11568705 · VCV3041539

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.405%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCC4-related disorder

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.64, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 185 kb · p 0.00034 · regional, not allelic
Overall
CADD	14.07	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 0.405% African / African-American · 304/75,028 alleles

Filtering AF 0.368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.353%

Overall 0.0502% 810/1,614,054 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.405%	247
Admixed American	0.155%	645
Remaining individualsnot grpmax-eligible	0.0752%	1,330
East Asian	0.0334%	2,992
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0292%	3,420
South Asian	0.00439%	22,766

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.Pro403Leu
Coding: c.1208C>T
MANE Select: NM_005845
dbSNP: rs11568705
Type: single nucleotide variant
Location: chr13:95194891 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 403: a UniProt-annotated variant site (in)

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

Disease context

ABCC4-related disorder

Similar variants

ABCC4 c.3871-5dup Likely benign same condition
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

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-pro403leu (accessed [today's date]).

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