Is BIRC7 p.Pro204Ser (c.610C>T) pathogenic?

BIRC7 p.Pro204Ser (c.610C>T) is classified Benign in BIRC7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-23). AlphaMissense: likely benign (0.0798); Common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BIRC7 p.Pro204Ser (c.610C>T)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

BIRC7 p.Pro204Ser

Q: How common is BIRC7 p.Pro204Ser (c.610C>T) in the general population?

BIRC7 p.Pro204Ser (c.610C>T) is common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.610C>T · rs11908302 · VCV781589

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.76	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 -0.49	GERP -2.1
Regional constraint	o/e 1.02	unconstrained · MANE · 3,505 bp · p 0.7 · regional, not allelic
Overall
CADD	4.304	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 10.3% African / African-American · 7,733/74,974 alleles

Filtering AF 10.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 10%

Overall 0.581% 9,374/1,612,818 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.3%	10
Middle Eastern	1.06%	95
Remaining individualsnot grpmax-eligible	0.816%	123
Admixed American	0.681%	147
Ashkenazi Jewishnot grpmax-eligible	0.581%	172
South Asian	0.0516%	1,938
European (non-Finnish)	0.0369%	2,706
Finnishnot grpmax-eligible	0.00318%	31,427
East Asian	0.00223%	44,856

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: BIRC7
Protein: p.Pro204Ser
Coding: c.610C>T
MANE Select: NM_139317
dbSNP: rs11908302
Type: single nucleotide variant
Location: chr20:63239194 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40 · 13 PDB
Residue 204: the 'disordered' region

Full BIRC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIRC7 p.Pro204Arg Uncertain significance ★ ⚠ same residue
BIRC7 p.Ala187Gly Benign ★★ same type
BIRC7 p.Ala273Val Uncertain significance ★ ⚠ same type
BIRC7 p.Arg156Trp Uncertain significance ★ ⚠ same type
BIRC7 p.Arg160Lys Uncertain significance ★ ⚠ same type
BIRC7 p.Arg244Trp Uncertain significance ★ ⚠ same type
BIRC7 p.Arg245Gln Uncertain significance ★ ⚠ same type
BIRC7 p.Arg245Trp 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/birc7-p-pro204ser (accessed [today's date]).

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