Is ABCC6 p.Arg899His (c.2696G>A) pathogenic?

ABCC6 p.Arg899His (c.2696G>A) is classified Likely benign in ABCC6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0705); Rare (popmax 0.387%, afr).

How common is ABCC6 p.Arg899His (c.2696G>A) in the general population?

ABCC6 p.Arg899His (c.2696G>A) is rare (popmax 0.387%, afr) (gnomAD).

What do computational predictors say about ABCC6 p.Arg899His (c.2696G>A)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

ABCC6 p.Arg899His

c.2696G>A · rs116355959 · VCV742983

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.387%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -2.1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	0.888	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 0.387% African / African-American · 290/74,986 alleles

Filtering AF 0.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.336%

Overall 0.0213% 343/1,614,032 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.387%	259
Admixed American	0.03%	3,334
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,251
East Asian	0.00669%	14,958
Finnishnot grpmax-eligible	0.00313%	31,998
European (non-Finnish)	0.00153%	65,556
South Asian	0.0011%	91,072

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: ABCC6
Protein: p.Arg899His
Coding: c.2696G>A
MANE Select: NM_001171
dbSNP: rs116355959
Type: single nucleotide variant
Location: chr16:16173375 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 899: the 'disordered' region

Full ABCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC6 p.Arg899Cys Likely benign ★★ ⚠ same residue
ABCC6 p.Arg899Ser Uncertain significance ★ ⚠ same residue
ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same type
ABCC6 c.2071-1G>A Likely pathogenic ★★ same type
ABCC6 c.2591-1G>T Likely pathogenic ★★ same type
ABCC6 c.2787+1G>T Pathogenic ★★ same type
ABCC6 c.3506+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC6 c.3507-1G>A Pathogenic ★★ 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/abcc6-p-arg899his (accessed [today's date]).

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