Is ABCC4 p.Ser323= (c.969A>G) pathogenic?

ABCC4 p.Ser323= (c.969A>G) is classified Benign in ABCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). Common (popmax 68.8%, afr) — too common for a highly-penetrant pathogenic allele.

ABCC4 p.Ser323=

Q: How common is ABCC4 p.Ser323= (c.969A>G) in the general population?

ABCC4 p.Ser323= (c.969A>G) is common (popmax 68.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.969A>G · VCV4683820

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 68.8%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP -13	GERP -3.1
Overall
CADD	0.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.8% African / African-American · 51,574/74,932 alleles

Filtering AF 68.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 68.1%

Overall 65.3% 1,054,134/1,613,838 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	68.8%	1
European (non-Finnish)	66.4%	2
South Asian	64.3%	2
Finnishnot grpmax-eligible	63.6%	2
Remaining individualsnot grpmax-eligible	63.4%	2
Amishnot grpmax-eligible	62.2%	2
Admixed American	58%	2
Middle Eastern	56.8%	2
East Asian	55.5%	2
Ashkenazi Jewishnot grpmax-eligible	54.4%	2

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.Ser323=
Coding: c.969A>G
MANE Select: NM_005845
Type: single nucleotide variant
Location: chr13:95206724 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 323: an α-helix; the abc transmembrane type-1 1 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-ser323 (accessed [today's date]).

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