Is RCSD1 p.Pro42Ser (c.124C>T) pathogenic?

RCSD1 p.Pro42Ser (c.124C>T) is classified Uncertain significance in RCSD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: ambiguous (0.5017); Very rare (popmax 0.00769%, sas).

How common is RCSD1 p.Pro42Ser (c.124C>T) in the general population?

RCSD1 p.Pro42Ser (c.124C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about RCSD1 p.Pro42Ser (c.124C>T)?

AlphaMissense predicts ambiguous (score 0.5017) — an in-silico prediction, not a clinical call.

RCSD1 p.Pro42Ser

c.124C>T · VCV3313442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5017 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Computational evidence

Protein change
AlphaMissense	0.5017	ambiguous
REVEL	0.319	indeterminate
SaProt	LLR -11.07	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 74 kb · p 0.063 · regional, not allelic
Overall
CADD	24.3	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 0.00769% South Asian · 7/91,054 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000496% 8/1,613,728 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,008
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Pro42Ser
Coding: c.124C>T
MANE Select: NM_052862
Type: single nucleotide variant
Location: chr1:167685436 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.03
Residue 42: 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-pro42ser (accessed [today's date]).

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