Is RCSD1 p.Ser192Pro (c.574T>C) pathogenic?

RCSD1 p.Ser192Pro (c.574T>C) is classified Likely benign in RCSD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: likely benign (0.0628); Ultra-rare (popmax 0.0234%, amr).

How common is RCSD1 p.Ser192Pro (c.574T>C) in the general population?

RCSD1 p.Ser192Pro (c.574T>C) is ultra-rare (popmax 0.0234%, amr) (gnomAD).

What do computational predictors say about RCSD1 p.Ser192Pro (c.574T>C)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

RCSD1 p.Ser192Pro

c.574T>C · rs754459738 · VCV2410765

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0234%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.67	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 -1	GERP -3.9
Regional constraint	o/e 1.08	unconstrained · MANE · 74 kb · p 0.063 · regional, not allelic
Overall
CADD	1.091	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 0.0234% Admixed American · 14/59,952 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00155% 25/1,613,562 alleles · ultra-rare exomes 23/1,461,894 · genomes 2/151,668 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0234%	4,282
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000848%	117,993

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: RCSD1
Protein: p.Ser192Pro
Coding: c.574T>C
MANE Select: NM_052862
dbSNP: rs754459738
Type: single nucleotide variant
Location: chr1:167697198 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.03
Residue 192: the 'disordered' region

Full RCSD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RCSD1 p.Ala137Thr Uncertain significance ★ ⚠ same type
RCSD1 p.Ala16Thr Uncertain significance ★ ⚠ same type
RCSD1 p.Ala213Thr Uncertain significance ★ ⚠ same type
RCSD1 p.Ala21Gly Uncertain significance ★ ⚠ same type
RCSD1 p.Ala224Val Uncertain significance ★ ⚠ same type
RCSD1 p.Ala234Ser Uncertain significance ★ ⚠ same type
RCSD1 p.Ala31Val Uncertain significance ★ ⚠ same type
RCSD1 p.Ala33Val 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/rcsd1-p-ser192pro (accessed [today's date]).

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