Is ABCC1 p.Ser92Phe (c.275C>T) pathogenic?

ABCC1 p.Ser92Phe (c.275C>T) is classified Benign in ABCC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-16). AlphaMissense: ambiguous (0.5107); Rare (popmax 0.453%, afr); Associated with ABCC1-related disorder.

What condition is associated with ABCC1 p.Ser92Phe (c.275C>T)?

ABCC1 p.Ser92Phe (c.275C>T) is associated with ABCC1-related disorder (ClinVar).

How common is ABCC1 p.Ser92Phe (c.275C>T) in the general population?

ABCC1 p.Ser92Phe (c.275C>T) is rare (popmax 0.453%, afr) (gnomAD).

What do computational predictors say about ABCC1 p.Ser92Phe (c.275C>T)?

AlphaMissense predicts ambiguous (score 0.5107) — an in-silico prediction, not a clinical call.

ABCC1 p.Ser92Phe

c.275C>T · rs8187844 · VCV3053129

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5107 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.453%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

ABCC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.5107	ambiguous
REVEL	0.264	benign-leaning
SaProt	LLR -9.76	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 95 kb · p 0.48 · regional, not allelic
Overall
CADD	26.6	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 0.453% African / African-American · 339/74,876 alleles

Filtering AF 0.413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.397%

Overall 0.0231% 372/1,611,656 alleles · rare exomes 189/1,459,488 · genomes 183/152,168 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.453%	221
Remaining individualsnot grpmax-eligible	0.0256%	3,900
Admixed American	0.0168%	5,959
South Asian	0.00332%	30,154
European (non-Finnish)	0.000339%	294,776

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.Ser92Phe
Coding: c.275C>T
MANE Select: NM_004996
dbSNP: rs8187844
Type: single nucleotide variant
Location: chr16:16009825 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 5 PDB

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

Disease context

ABCC1-related disorder

Similar variants

ABCC1 p.Arg62Gln Benign same condition
ABCC1 p.Arg633Gln Likely benign same condition
ABCC1 p.Asn412Ser Likely benign same condition
ABCC1 p.Gly639Trp Likely benign same condition
ABCC1 p.Pro285Leu Likely benign same condition
ABCC1 p.Thr1401Met Likely benign same condition
ABCC1 p.Val1481Ile Benign same condition
ABCC1 p.Thr1464Met 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/abcc1-p-ser92phe (accessed [today's date]).

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