Is SORT1 p.Ile124Val (c.370A>G) pathogenic?

SORT1 p.Ile124Val (c.370A>G) is classified Likely benign in SORT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). AlphaMissense: likely benign (0.1424); Low-frequency (popmax 2.54%, mid).

How common is SORT1 p.Ile124Val (c.370A>G) in the general population?

SORT1 p.Ile124Val (c.370A>G) is low-frequency (popmax 2.54%, mid) (gnomAD).

What do computational predictors say about SORT1 p.Ile124Val (c.370A>G)?

AlphaMissense predicts likely benign (score 0.1424) — an in-silico prediction, not a clinical call.

SORT1 p.Ile124Val

c.370A>G · rs61797119 · VCV2638981

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1424 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.54%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1424	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 0.6, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 84 kb · p 1.9e-12 · regional, not allelic
Overall
CADD	18.61	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 2.54% Middle Eastern · 153/6,012 alleles

Filtering AF 2.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.09%

Overall 0.38% 6,047/1,591,560 alleles · low-frequency exomes 5,538/1,439,276 · genomes 509/152,284 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.54%	39
Ashkenazi Jewishnot grpmax-eligible	1.69%	59
Remaining individualsnot grpmax-eligible	0.491%	204
Admixed American	0.408%	245
European (non-Finnish)	0.392%	255
South Asian	0.204%	491
African / African-American	0.103%	968
Finnishnot grpmax-eligible	0.0579%	1,727

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: SORT1
Protein: p.Ile124Val
Coding: c.370A>G
MANE Select: NM_002959
dbSNP: rs61797119
Type: single nucleotide variant
Location: chr1:109367478 (GRCh38)
Gene constraint: LOEUF 0.553 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 83.27 · 17 PDB
Residue 124: the '10-bladed beta-propeller' region; the vps10p domain; a β-strand

Full SORT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SORT1 p.Asp358Tyr Benign ★★ ⚠ same type
SORT1 p.Ser746Asn Benign ★★ same type
SORT1 p.Ala340Thr Uncertain significance ★ ⚠ same type
SORT1 p.Arg288Lys Uncertain significance ★ ⚠ same type
SORT1 p.Arg311His Uncertain significance ★ ⚠ same type
SORT1 p.Arg326Ser Uncertain significance ★ ⚠ same type
SORT1 p.Arg382Gln Uncertain significance ★ ⚠ same type
SORT1 p.Arg392Leu 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/sort1-p-ile124val (accessed [today's date]).

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