Is ABCC11 p.Arg235Gln (c.704G>A) pathogenic?

ABCC11 p.Arg235Gln (c.704G>A) is classified Uncertain significance in ABCC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). AlphaMissense: likely benign (0.1148); Very rare (popmax 0.00329%, sas).

How common is ABCC11 p.Arg235Gln (c.704G>A) in the general population?

ABCC11 p.Arg235Gln (c.704G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ABCC11 p.Arg235Gln (c.704G>A)?

AlphaMissense predicts likely benign (score 0.1148) — an in-silico prediction, not a clinical call.

ABCC11 p.Arg235Gln

c.704G>A · rs191605136 · VCV3127659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1148 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1148	likely benign
REVEL	0.368	indeterminate
SaProt	LLR -9.62	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 -0.82	GERP -5
Regional constraint	o/e 0.98	unconstrained · MANE · 65 kb · p 0.31 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00235% 38/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
European (non-Finnish)	0.00263%	38,066
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,026
African / African-American	0.00134%	74,906

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: ABCC11
Protein: p.Arg235Gln
Coding: c.704G>A
MANE Select: NM_001370497
dbSNP: rs191605136
Type: single nucleotide variant
Location: chr16:48222671 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.30
Residue 235: the abc transmembrane type-1 1 domain

Full ABCC11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC11 p.Ala414= Benign ★★ same type
ABCC11 p.Arg630Trp Likely benign ★★ ⚠ same type
ABCC11 p.Leu553= Benign ★★ same type
ABCC11 p.Met970Val Benign ★★ same type
ABCC11 p.Pro78Ser Benign ★★ same type
ABCC11 p.Thr1328= Benign ★★ same type
ABCC11 p.Thr546Met Benign ★★ same type
ABCC11 p.Trp8Cys 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/abcc11-p-arg235gln (accessed [today's date]).

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