Is STRC p.Ser332Cys (c.995C>G) pathogenic?

STRC p.Ser332Cys (c.995C>G) is classified Uncertain significance in STRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-12). AlphaMissense: likely benign (0.1427); Ultra-rare (popmax 0.0686%, sas).

How common is STRC p.Ser332Cys (c.995C>G) in the general population?

STRC p.Ser332Cys (c.995C>G) is ultra-rare (popmax 0.0686%, sas) (gnomAD).

What do computational predictors say about STRC p.Ser332Cys (c.995C>G)?

AlphaMissense predicts likely benign (score 0.1427) — an in-silico prediction, not a clinical call.

STRC p.Ser332Cys

c.995C>G · rs1360568237 · VCV506243

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1427 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0686%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1427	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -6.64	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 6.6	GERP -0.26, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0686% South Asian · 31/45,160 alleles

Filtering AF 0.0497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0432%

Overall 0.00762% 34/446,364 alleles · ultra-rare exomes 33/421,528 · genomes 1/24,836 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0686%	1,457
Middle Eastern	0.0493%	2,030
Remaining individualsnot grpmax-eligible	0.00805%	12,419

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: STRC
Protein: p.Ser332Cys
Coding: c.995C>G
MANE Select: NM_153700
dbSNP: rs1360568237
Type: single nucleotide variant
Location: chr15:43616571 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.21

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

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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/strc-p-ser332cys (accessed [today's date]).

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