Is STRC p.Leu191Val (c.571C>G) pathogenic?

STRC p.Leu191Val (c.571C>G) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely benign (0.0911); Ultra-rare (popmax 0.033%, sas); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Leu191Val (c.571C>G)?

STRC p.Leu191Val (c.571C>G) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Leu191Val (c.571C>G) in the general population?

STRC p.Leu191Val (c.571C>G) is ultra-rare (popmax 0.033%, sas) (gnomAD).

What do computational predictors say about STRC p.Leu191Val (c.571C>G)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

STRC p.Leu191Val

c.571C>G · rs776841761 · VCV3171615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -7.62	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 3.2	GERP 2, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	19.79	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 0.033% South Asian · 30/90,982 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00354% 57/1,610,460 alleles · ultra-rare exomes 53/1,460,512 · genomes 4/149,948 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.033%	3,033
Middle Eastern	0.0166%	6,020
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,526
European (non-Finnish)	0.00195%	51,217
Remaining individualsnot grpmax-eligible	0.0016%	62,414
African / African-American	0.00135%	74,338

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.Leu191Val
Coding: c.571C>G
MANE Select: NM_153700
dbSNP: rs776841761
Type: single nucleotide variant
Location: chr15:43617850 (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

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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
STRC p.Cys1464Tyr 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-leu191val (accessed [today's date]).

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