Is STRC p.Ser1701Arg (c.5101A>C) pathogenic?

STRC p.Ser1701Arg (c.5101A>C) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely pathogenic (0.6809); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Ser1701Arg (c.5101A>C)?

STRC p.Ser1701Arg (c.5101A>C) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Ser1701Arg (c.5101A>C) in the general population?

STRC p.Ser1701Arg (c.5101A>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about STRC p.Ser1701Arg (c.5101A>C)?

AlphaMissense predicts likely pathogenic (score 0.6809) — an in-silico prediction, not a clinical call.

STRC p.Ser1701Arg

c.5101A>C · VCV3450854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6809	likely pathogenic
REVEL	0.576	indeterminate
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.3	GERP 2, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 559 bp · p 2.3e-14 · regional, not allelic
Overall
CADD	24.0	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 0.00446% East Asian · 2/44,842 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000186% 3/1,612,966 alleles · very rare exomes 3/1,461,464 · genomes 0/151,502 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,421
Remaining individualsnot grpmax-eligible	0.0016%	62,464

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.Ser1701Arg
Coding: c.5101A>C
MANE Select: NM_153700
Type: single nucleotide variant
Location: chr15:43600098 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC p.Ser1701Ile Uncertain significance ★ same residue
STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1102Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg1237Trp Uncertain significance ★★ ⚠ same condition
STRC p.Arg1338Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg56His Uncertain significance ★★ ⚠ same condition
STRC p.Arg832Trp Uncertain significance ★★ same condition
STRC p.Arg92Gln Uncertain significance ★★ ⚠ same condition

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-ser1701arg (accessed [today's date]).

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