Is CYREN p.Pro120Ala (c.358C>G) pathogenic?

CYREN p.Pro120Ala (c.358C>G) is classified Likely benign in CYREN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely benign (0.0571); Rare (popmax 0.121%, afr).

How common is CYREN p.Pro120Ala (c.358C>G) in the general population?

CYREN p.Pro120Ala (c.358C>G) is rare (popmax 0.121%, afr) (gnomAD).

What do computational predictors say about CYREN p.Pro120Ala (c.358C>G)?

AlphaMissense predicts likely benign (score 0.0571) — an in-silico prediction, not a clinical call.

CYREN p.Pro120Ala

c.358C>G · rs143708624 · VCV3079783

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0571 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0571	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -6.01	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 0.22	GERP -2.5
Regional constraint	o/e 1.09	unconstrained · MANE · 2,308 bp · p 0.23 · regional, not allelic
Overall
CADD	1.488	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 0.121% African / African-American · 91/75,048 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0936%

Overall 0.00601% 97/1,613,926 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.121%	825
Remaining individualsnot grpmax-eligible	0.0048%	20,834
Admixed American	0.00333%	30,016
East Asian	0.00223%	44,884

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: CYREN
Protein: p.Pro120Ala
Coding: c.358C>G
MANE Select: NM_024033
dbSNP: rs143708624
Type: single nucleotide variant
Location: chr7:135166727 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.81 · 1 PDB
Residue 120: the 'disordered' region

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

Similar variants

CYREN p.Lys149= Benign ★★ same type
CYREN p.Asp112His Uncertain significance ★ ⚠ same type
TMEM140 p.Ala104Gly Uncertain significance ★ ⚠ same type
TMEM140 p.Ala153Pro Uncertain significance ★ ⚠ same type
TMEM140 p.Arg174Lys Uncertain significance ★ ⚠ same type
TMEM140 p.Arg5Lys Uncertain significance ★ ⚠ same type
TMEM140 p.Asp41Glu Uncertain significance ★ ⚠ same type
TMEM140 p.Gln105Glu 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/cyren-p-pro120ala (accessed [today's date]).

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