Is ABCC4 p.Met184Thr (c.551T>C) pathogenic?

ABCC4 p.Met184Thr (c.551T>C) is classified Likely benign in ABCC4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-09). AlphaMissense: likely benign (0.0577); Rare (popmax 0.644%, afr).

How common is ABCC4 p.Met184Thr (c.551T>C) in the general population?

ABCC4 p.Met184Thr (c.551T>C) is rare (popmax 0.644%, afr) (gnomAD).

What do computational predictors say about ABCC4 p.Met184Thr (c.551T>C)?

AlphaMissense predicts likely benign (score 0.0577) — an in-silico prediction, not a clinical call.

ABCC4 p.Met184Thr

c.551T>C · rs45454092 · VCV712838

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0577 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.644%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0577	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -3.69	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 -1.1	GERP -0.8
Regional constraint	o/e 0.92	unconstrained · MANE · 93 kb · p 0.13 · regional, not allelic
Overall
CADD	1.042	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 0.644% African / African-American · 483/75,058 alleles

Filtering AF 0.596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.577%

Overall 0.0334% 539/1,614,056 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.644%	155
Admixed American	0.0333%	3,001
Remaining individualsnot grpmax-eligible	0.0256%	3,907
South Asian	0.00439%	22,766
European (non-Finnish)	0.00136%	73,744

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.Met184Thr
Coding: c.551T>C
MANE Select: NM_005845
dbSNP: rs45454092
Type: single nucleotide variant
Location: chr13:95210762 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 184: an α-helix; the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in)

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-met184thr (accessed [today's date]).

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