Is CHGA p.Ser105Pro (c.313T>C) pathogenic?

CHGA p.Ser105Pro (c.313T>C) is classified Uncertain significance in CHGA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely benign (0.2495); Ultra-rare (popmax 0.0165%, mid).

How common is CHGA p.Ser105Pro (c.313T>C) in the general population?

CHGA p.Ser105Pro (c.313T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CHGA p.Ser105Pro (c.313T>C)?

AlphaMissense predicts likely benign (score 0.2495) — an in-silico prediction, not a clinical call.

CHGA p.Ser105Pro

c.313T>C · rs1566674156 · VCV2394874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2495 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2495	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -12.45	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP 0.73, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 12 kb · p 0.79 · regional, not allelic
Overall
CADD	20.3	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 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000744% 12/1,613,440 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
African / African-American	0.0107%	9,362
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	8.47e-05%	1,180,025

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: CHGA
Protein: p.Ser105Pro
Coding: c.313T>C
MANE Select: NM_001275
dbSNP: rs1566674156
Type: single nucleotide variant
Location: chr14:92929773 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.33 · 2 PDB
Residue 105: the 'disordered' region

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

Similar variants

CHGA p.Ala225Thr Uncertain significance ★ ⚠ same type
CHGA p.Ala380Ser Uncertain significance ★ ⚠ same type
CHGA p.Ala425Thr Uncertain significance ★ ⚠ same type
CHGA p.Ala83Thr Uncertain significance ★ same type
CHGA p.Ala87Asp Uncertain significance ★ ⚠ same type
CHGA p.Arg357Trp Uncertain significance ★ ⚠ same type
CHGA p.Arg377Gln Uncertain significance ★ ⚠ same type
CHGA p.Arg377Pro 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/chga-p-ser105pro (accessed [today's date]).

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