Is ABCC4 p.Phe948= (c.2844T>C) pathogenic?

ABCC4 p.Phe948= (c.2844T>C) is classified Benign in ABCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). Common (popmax 95.9%, nfe) — too common for a highly-penetrant pathogenic allele.

ABCC4 p.Phe948=

Q: How common is ABCC4 p.Phe948= (c.2844T>C) in the general population?

ABCC4 p.Phe948= (c.2844T>C) is common (popmax 95.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2844T>C · VCV4683810

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 95.9%, nfe) — 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 · A>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.3	GERP -4
Overall
CADD	0.481	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 95.9% European (non-Finnish) · 1,131,419/1,179,778 alleles

Filtering AF 95.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 95.7%

Overall 94.8% 1,529,845/1,613,470 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	96.1%	1
European (non-Finnish)grpmax	95.9%	1
South Asian	95.5%	1
Middle Eastern	95.1%	1
Remaining individualsnot grpmax-eligible	94.3%	1
Amishnot grpmax-eligible	94%	1
Admixed American	93.6%	1
Finnishnot grpmax-eligible	91.6%	1
African / African-American	91.5%	1
East Asian	76.7%	1

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe948=
Coding: c.2844T>C
MANE Select: NM_005845
Type: single nucleotide variant
Location: chr13:95074287 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 948: 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-phe948 (accessed [today's date]).

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