Is ABCC1 p.Ser465Cys (c.1394C>G) pathogenic?

ABCC1 p.Ser465Cys (c.1394C>G) is classified Uncertain significance in ABCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: likely benign (0.3323); Very rare (popmax 0.00533%, afr).

How common is ABCC1 p.Ser465Cys (c.1394C>G) in the general population?

ABCC1 p.Ser465Cys (c.1394C>G) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about ABCC1 p.Ser465Cys (c.1394C>G)?

AlphaMissense predicts likely benign (score 0.3323) — an in-silico prediction, not a clinical call.

ABCC1 p.Ser465Cys

c.1394C>G · VCV3540947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3323 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3323	likely benign
REVEL	0.638	indeterminate
SaProt	LLR -14.11	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.88	unconstrained · MANE · 97 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	24.4	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 0.00533% African / African-American · 4/75,046 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00041% 6/1,461,868 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,762
Remaining individualsnot grpmax-eligible	0.0016%	62,510
South Asian	0.0011%	91,082

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: ABCC1
Protein: p.Ser465Cys
Coding: c.1394C>G
MANE Select: NM_004996
Type: single nucleotide variant
Location: chr16:16052737 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 5 PDB
Residue 465: the abc transmembrane type-1 1 domain

Full ABCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC1 p.Ser465= Likely benign ★ same residue
ABCC1 p.Thr1464Met Uncertain significance ★★ ⚠ same type
ABCC1 c.1381-5C>G Benign ★★ same type
ABCC1 p.Ala1260= Benign ★★ same type
ABCC1 p.Ala1406= Benign ★★ same type
ABCC1 p.Arg433Ser Benign ★★ same type
ABCC1 p.Asp637= Likely benign ★★ same type
ABCC1 p.Gly762= Benign/Likely 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/abcc1-p-ser465cys (accessed [today's date]).

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