Is ABCC6 p.Val37Phe (c.109G>T) pathogenic?

ABCC6 p.Val37Phe (c.109G>T) is classified Likely benign in ABCC6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1033); Rare (popmax 0.827%, eas).

How common is ABCC6 p.Val37Phe (c.109G>T) in the general population?

ABCC6 p.Val37Phe (c.109G>T) is rare (popmax 0.827%, eas) (gnomAD).

What do computational predictors say about ABCC6 p.Val37Phe (c.109G>T)?

AlphaMissense predicts likely benign (score 0.1033) — an in-silico prediction, not a clinical call.

ABCC6 p.Val37Phe

c.109G>T · rs557779326 · VCV763891

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1033 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.827%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1033	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -5.49	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 0.38	GERP 0.51, phastCons 0.012
Regional constraint	o/e 0.95	unconstrained · MANE · 158 bp · p 0.68 · regional, not allelic
Overall
CADD	17.17	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 0.827% East Asian · 371/44,870 alleles

Filtering AF 0.757% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.73%

Overall 0.0235% 380/1,613,722 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.827%	121
Remaining individualsnot grpmax-eligible	0.0096%	10,413
Admixed American	0.00167%	59,964
South Asian	0.0011%	91,060
European (non-Finnish)	8.48e-05%	1,179,754

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.Val37Phe
Coding: c.109G>T
MANE Select: NM_001171
dbSNP: rs557779326
Type: single nucleotide variant
Location: chr16:16221759 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB

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

Similar variants

ABCC6 p.Val37= Uncertain significance ★ same residue
ABCC6 p.Val37fs Pathogenic/Likely pathogenic ★★ 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-val37phe (accessed [today's date]).

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