Is ABCC4 p.Lys304Asn (c.912G>T) pathogenic?

ABCC4 p.Lys304Asn (c.912G>T) is classified Benign in ABCC4 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-28). AlphaMissense: likely benign (0.2332); Common (popmax 21.4%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ABCC4 p.Lys304Asn (c.912G>T)?

AlphaMissense predicts likely benign (score 0.2332) — an in-silico prediction, not a clinical call.

ABCC4 p.Lys304Asn

Q: How common is ABCC4 p.Lys304Asn (c.912G>T) in the general population?

ABCC4 p.Lys304Asn (c.912G>T) is common (popmax 21.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.912G>T · VCV4393868

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2332 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 21.4%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2332	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.29	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.41	GERP -0.54, phastCons 0.99
Regional constraint	o/e 0.59	unconstrained · MANE · 1,333 bp · p 1.8e-06 · regional, not allelic
Overall
CADD	21.8	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 21.4% East Asian · 9,577/44,838 alleles

Filtering AF 21% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.9%

Overall 8.25% 133,071/1,613,542 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	21.4%	5
African / African-American	17%	6
South Asian	13.5%	7
Ashkenazi Jewishnot grpmax-eligible	13.3%	8
Middle Eastern	11.4%	9
Remaining individualsnot grpmax-eligible	9.66%	10
Admixed American	8.91%	11
European (non-Finnish)	6.64%	15
Finnishnot grpmax-eligible	6.26%	16
Amishnot grpmax-eligible	1.43%	70

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.Lys304Asn
Coding: c.912G>T
MANE Select: NM_005845
Type: single nucleotide variant
Location: chr13:95206781 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 304: an α-helix; the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (transport properties comparable to wild-type)

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-lys304asn (accessed [today's date]).

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