Is ABCC10 p.Glu718Asp (c.2154G>T) pathogenic?

ABCC10 p.Glu718Asp (c.2154G>T) is classified Uncertain significance in ABCC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-03). AlphaMissense: likely benign (0.3273); Very rare (popmax 0.00661%, nfe).

How common is ABCC10 p.Glu718Asp (c.2154G>T) in the general population?

ABCC10 p.Glu718Asp (c.2154G>T) is very rare (popmax 0.00661%, nfe) (gnomAD).

What do computational predictors say about ABCC10 p.Glu718Asp (c.2154G>T)?

AlphaMissense predicts likely benign (score 0.3273) — an in-silico prediction, not a clinical call.

ABCC10 p.Glu718Asp

c.2154G>T · rs1053808601 · VCV2289040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3273 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3273	likely benign
REVEL	0.683	pathogenic-leaning
SaProt	LLR -12.39	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -3.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 22 kb · p 4.2e-06 · regional, not allelic
Overall
CADD	22.4	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 0.00661% European (non-Finnish) · 78/1,179,882 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00496% 80/1,613,722 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00661%	15,127
Remaining individualsnot grpmax-eligible	0.0032%	31,223

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: ABCC10
Protein: p.Glu718Asp
Coding: c.2154G>T
MANE Select: NM_001198934
dbSNP: rs1053808601
Type: single nucleotide variant
Location: chr6:43441888 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32
Residue 718: the abc transporter 1 domain

Full ABCC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC10 p.Met895Thr Uncertain significance ★★ ⚠ same type
ABCC10 p.Ala1050Ser Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1119Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1165Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1179Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1324Pro Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1324Ser Uncertain significance ★ ⚠ same type
ABCC10 p.Ala144Gly Uncertain significance ★ ⚠ 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/abcc10-p-glu718asp (accessed [today's date]).

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