Is SDC2 p.Ile150Thr (c.449T>C) pathogenic?

SDC2 p.Ile150Thr (c.449T>C) is classified Uncertain significance in SDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely pathogenic (0.6527); Ultra-rare (popmax 0.0994%, sas).

How common is SDC2 p.Ile150Thr (c.449T>C) in the general population?

SDC2 p.Ile150Thr (c.449T>C) is ultra-rare (popmax 0.0994%, sas) (gnomAD).

What do computational predictors say about SDC2 p.Ile150Thr (c.449T>C)?

AlphaMissense predicts likely pathogenic (score 0.6527) — an in-silico prediction, not a clinical call.

SDC2 p.Ile150Thr

c.449T>C · rs143693366 · VCV2395107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6527 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0994%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6527	likely pathogenic
REVEL	0.675	pathogenic-leaning
SaProt	LLR -13.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 115 kb · p 0.45 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0994% South Asian · 90/90,518 alleles

Filtering AF 0.0828% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0766%

Overall 0.0127% 204/1,611,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0994%	1,006
Middle Eastern	0.0662%	1,512
Remaining individualsnot grpmax-eligible	0.0209%	4,795
European (non-Finnish)	0.00814%	12,278
East Asian	0.00224%	44,738

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: SDC2
Protein: p.Ile150Thr
Coding: c.449T>C
MANE Select: NM_002998
dbSNP: rs143693366
Type: single nucleotide variant
Location: chr8:96609391 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.79 · 1 PDB
Residue 150: an α-helix

Full SDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SDC2 p.Ile150Val Uncertain significance ★ ⚠ same residue
SDC2 p.Ser71Thr Benign ★★ same type
SDC2 p.Ala124Gly Uncertain significance ★ ⚠ same type
SDC2 p.Ala14Val Uncertain significance ★ ⚠ same type
SDC2 p.Arg170Cys Uncertain significance ★ ⚠ same type
SDC2 p.Arg170His Uncertain significance ★ ⚠ same type
SDC2 p.Arg184His Uncertain significance ★ ⚠ same type
SDC2 p.Arg72Gln 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/sdc2-p-ile150thr (accessed [today's date]).

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