Is SRP72 p.Pro166Ser (c.496C>T) pathogenic?

SRP72 p.Pro166Ser (c.496C>T) is classified Uncertain significance in SRP72 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-19). AlphaMissense: likely benign (0.152); Very rare (popmax 0.000763%, nfe).

How common is SRP72 p.Pro166Ser (c.496C>T) in the general population?

SRP72 p.Pro166Ser (c.496C>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about SRP72 p.Pro166Ser (c.496C>T)?

AlphaMissense predicts likely benign (score 0.152) — an in-silico prediction, not a clinical call.

SRP72 p.Pro166Ser

c.496C>T · VCV3364501

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.152 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.152	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -6.53	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	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 11 kb · p 0.58 · regional, not allelic
Overall
CADD	22.7	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 0.000763% European (non-Finnish) · 9/1,180,008 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,614,120 alleles · very rare exomes 9/1,461,816 · genomes 0/152,304 · joint denominator

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: SRP72
Protein: p.Pro166Ser
Coding: c.496C>T
MANE Select: NM_006947
Type: single nucleotide variant
Location: chr4:56474195 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.76 · 7 PDB

Full SRP72 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRP72 c.1502+1G>A Uncertain significance ★★ same type
SRP72 c.1640+4A>G Uncertain significance ★★ same type
SRP72 c.768-9T>G Uncertain significance ★★ same type
SRP72 p.Ala13Thr Uncertain significance ★★ ⚠ same type
SRP72 p.Ala156Gly Uncertain significance ★★ ⚠ same type
SRP72 p.Ala185Val Uncertain significance ★★ ⚠ same type
SRP72 p.Ala291Val Uncertain significance ★★ ⚠ same type
SRP72 p.Ala314Val 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/srp72-p-pro166ser (accessed [today's date]).

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