Is ABCA5 p.Ile986Val (c.2956A>G) pathogenic?

ABCA5 p.Ile986Val (c.2956A>G) is classified Likely benign in ABCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0816); Rare (popmax 0.222%, nfe).

How common is ABCA5 p.Ile986Val (c.2956A>G) in the general population?

ABCA5 p.Ile986Val (c.2956A>G) is rare (popmax 0.222%, nfe) (gnomAD).

What do computational predictors say about ABCA5 p.Ile986Val (c.2956A>G)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

ABCA5 p.Ile986Val

c.2956A>G · rs145300105 · VCV735846

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.222%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.277	benign-leaning
SaProt	LLR -6.13	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 0.85	GERP 0.28, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.22 · regional, not allelic
Overall
CADD	15.51	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 0.222% European (non-Finnish) · 2,614/1,174,990 alleles

Filtering AF 0.215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.177% 2,829/1,602,100 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.222%	449
Finnishnot grpmax-eligible	0.16%	626
Remaining individualsnot grpmax-eligible	0.113%	886
African / African-American	0.0322%	3,102
Admixed American	0.0277%	3,610
Middle Eastern	0.0167%	5,986
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,332
South Asian	0.00113%	88,296

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: ABCA5
Protein: p.Ile986Val
Coding: c.2956A>G
MANE Select: NM_172232
dbSNP: rs145300105
Type: single nucleotide variant
Location: chr17:69270687 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.12

Full ABCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA5 p.Ser288Phe Uncertain significance ★★ ⚠ same type
ABCA5 c.4765+3A>G Likely benign ★★ same type
ABCA5 p.Asn190Ser Likely benign ★★ ⚠ same type
ABCA5 p.Asn768Asp Benign ★★ same type
ABCA5 p.Asp817Tyr Likely benign ★★ ⚠ same type
ABCA5 p.Gly1159Arg Likely benign ★★ ⚠ same type
ABCA5 p.Gly128= Benign/Likely benign ★★ same type
ABCA5 p.Ile1173Val Likely 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/abca5-p-ile986val (accessed [today's date]).

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