Is SDC2 p.Ser71Thr (c.211T>A) pathogenic?

SDC2 p.Ser71Thr (c.211T>A) is classified Benign in SDC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-04-24). AlphaMissense: likely benign (0.072); Common (popmax 39%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about SDC2 p.Ser71Thr (c.211T>A)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

SDC2 p.Ser71Thr

Q: How common is SDC2 p.Ser71Thr (c.211T>A) in the general population?

SDC2 p.Ser71Thr (c.211T>A) is common (popmax 39%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.211T>A · rs1042381 · VCV1288543

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 39%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.90	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 2.3	GERP 1.3, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 115 kb · p 0.45 · regional, not allelic
Overall
CADD	18.91	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 39% African / African-American · 29,191/74,906 alleles

Filtering AF 38.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.4%

Overall 19.2% 310,010/1,613,670 alleles · common exomes 274,033/1,461,574 · genomes 35,977/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	39%	3
East Asian	20.4%	5
Remaining individualsnot grpmax-eligible	19.3%	5
European (non-Finnish)	19%	5
Middle Eastern	18.4%	5
Ashkenazi Jewishnot grpmax-eligible	17%	6
Finnishnot grpmax-eligible	15.6%	6
Amishnot grpmax-eligible	15.5%	6
South Asian	13.3%	8
Admixed American	12.4%	8

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.Ser71Thr
Coding: c.211T>A
MANE Select: NM_002998
dbSNP: rs1042381
Type: single nucleotide variant
Location: chr8:96602433 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.79 · 1 PDB
Residue 71: a UniProt-annotated variant site (in)

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

Similar variants

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
SDC2 p.Asn95Lys Uncertain significance ★ ⚠ same type
SDC2 p.Asp29Asn 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-ser71thr (accessed [today's date]).

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