Is ABCC4 p.Val854Phe (c.2560G>T) pathogenic?

ABCC4 p.Val854Phe (c.2560G>T) is classified Likely benign in ABCC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.3121); Low-frequency (popmax 3.01%, sas).

How common is ABCC4 p.Val854Phe (c.2560G>T) in the general population?

ABCC4 p.Val854Phe (c.2560G>T) is low-frequency (popmax 3.01%, sas) (gnomAD).

What do computational predictors say about ABCC4 p.Val854Phe (c.2560G>T)?

AlphaMissense predicts likely benign (score 0.3121) — an in-silico prediction, not a clinical call.

ABCC4 p.Val854Phe

c.2560G>T · VCV4683813

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3121 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.01%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3121	likely benign
REVEL	0.524	indeterminate
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -1.8, phastCons 0.005
Regional constraint	o/e 0.89	unconstrained · MANE · 185 kb · p 0.00034 · regional, not allelic
Overall
CADD	13.13	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 3.01% South Asian · 2,740/91,044 alleles

Filtering AF 2.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.88%

Overall 0.78% 12,589/1,613,880 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	3.01%	33
Middle Eastern	0.876%	114
Remaining individualsnot grpmax-eligible	0.83%	120
European (non-Finnish)	0.745%	134
Amishnot grpmax-eligible	0.658%	152
Ashkenazi Jewishnot grpmax-eligible	0.429%	233
Admixed American	0.357%	280
African / African-American	0.109%	915
Finnishnot grpmax-eligible	0.0875%	1,143
East Asian	0.00446%	22,429

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.Val854Phe
Coding: c.2560G>T
MANE Select: NM_005845
Type: single nucleotide variant
Location: chr13:95083266 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 25 PDB
Residue 854: an α-helix; the abc transmembrane type-1 2 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-val854phe (accessed [today's date]).

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